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1/S cyclin-dependent kinases
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of outstanding interest. See annotation to [13].
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1/S cyclin-dependent kinases. of outstanding interest J Biol Chem. 272:1997;12738-12746 See annotation to [13].
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Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin/cdk complexes
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of special interest. These two papers [16,17] provide biological support for the notion that different aspects of pRB function are regulated by distinct phosphorylation events.
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Mol Cell Biol
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Lundberg, A.S.1
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Kuo M-H1
Allis, C.D.2
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20
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0032484989
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Retinoblastoma protein recruits histone deacetylase to repress transcription
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of outstanding interest. Together these three papers [20-22] suggest that at least one mechanism by which pRB-E2F complexes mediate transcriptional repression is through binding to a histone deacetylase activity. HDAC1 is shown to contain a functional LxCxE (in the single letter code for amino acids where x is any amino acid) motif, suggesting that it may be a target of the transforming viral oncoproteins such as SV40 T antigen, HPV E7 and Adenovirus E1a.
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Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T. Retinoblastoma protein recruits histone deacetylase to repress transcription. of outstanding interest Nature. 391:1998;597-601 Together these three papers [20-22] suggest that at least one mechanism by which pRB-E2F complexes mediate transcriptional repression is through binding to a histone deacetylase activity. HDAC1 is shown to contain a functional LxCxE (in the single letter code for amino acids where x is any amino acid) motif, suggesting that it may be a target of the transforming viral oncoproteins such as SV40 T antigen, HPV E7 and Adenovirus E1a.
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Nature
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Brehm, A.1
Miska, E.A.2
McCance, D.J.3
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Bannister, A.J.5
Kouzarides, T.6
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21
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0032484904
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Retinoblastoma protein represses transcription by recruiting a histone deacetylase
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of outstanding interest. See annotation to [20].
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Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain JP, Troalen F, Trouche D, Harel-Bellan A. Retinoblastoma protein represses transcription by recruiting a histone deacetylase. of outstanding interest Nature. 391:1998;601-605 See annotation to [20].
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Magnaghi-Jaulin, L.1
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Trouche, D.8
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Rb interacts with histone deacetylase to repress transcription
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of outstanding interest. See annotation to [20].
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Luo RX, Postigio AA, Dean DC. Rb interacts with histone deacetylase to repress transcription. of outstanding interest Cell. 92:1998;463-473 See annotation to [20].
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Luo, R.X.1
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31
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Stable binding of E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumour cell growth
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of special interest. This paper provides evidence that the induction of differentiation and cell cycle arrest by pRB are separate events. It follows from this that both pRB induced differentiation and cell cycle arrest might contribute independently to tumor suppression, and evidence for this is provided. It also follows that cell cycle arrest and differentiation are mediated by distinct molecular mechanisms and evidence for this was obtained.
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Sellers WR, Novitch BG, Miyake S, Heith A, Otterson GA, Kaye FJ, Lassar AB, Kaelin WGJ Jr. Stable binding of E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumour cell growth. of special interest Genes Dev. 12:1998;95-106 This paper provides evidence that the induction of differentiation and cell cycle arrest by pRB are separate events. It follows from this that both pRB induced differentiation and cell cycle arrest might contribute independently to tumor suppression, and evidence for this is provided. It also follows that cell cycle arrest and differentiation are mediated by distinct molecular mechanisms and evidence for this was obtained.
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Sellers, W.R.1
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Kaye, F.J.6
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Kaelin W.G.J., Jr.8
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32
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Regulation of p53 stability by mdm2
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of outstanding interest. These papers [32,33] are significant because they demonstrate that mdm2 is a key determinant of p53 stability. Since p53 activity is thought to be regulated in large part through the stability of the protein, they suggest that the signal transduction pathways that activate p53 in response to DNA damage or activation of cellular oncogenes might feed through mdm2.
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Kubbutat MHG, Jones SN, Vousden KH. Regulation of p53 stability by mdm2. of outstanding interest Nature. 387:1997;299-303 These papers [32,33] are significant because they demonstrate that mdm2 is a key determinant of p53 stability. Since p53 activity is thought to be regulated in large part through the stability of the protein, they suggest that the signal transduction pathways that activate p53 in response to DNA damage or activation of cellular oncogenes might feed through mdm2.
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Nature
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Kubbutat, M.H.G.1
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Mdm2 promotes the rapid degradation of p53
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of outstanding interest. See annotation to [32].
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Nature
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38
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39
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Alternative reading frames of the INK4a tumour suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest
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Sherr, C.J.4
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40
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0032146795
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E1a signalling to p53 involves the p19ARF tumour suppressor
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of outstanding interest. These papers [40,41] confirm the concepts implicit in [42-44]. That is, that a signal transduction cascade feeds through p19ARF and mdm2 to activate p53 in response to activation of oncogenes. Interestingly, [44] showed that the role of p19ARF in activation of p53 is restricted to activation by oncogenes and it is not required for activation by DNA damage. This implies that oncogenes activate p53 in a manner that is independent of any capacity that they have to cause DNA damage.
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de Stanchina E, McCurrach ME, Zindy F, Shieh S-Y, Ferbeyre G, Samuelson AV, Prives C, Roussel M, Sherr CJ, Lowe SW. E1a signalling to p53 involves the p19ARF tumour suppressor. of outstanding interest Genes Dev. 12:1998;2434-2442 These papers [40,41] confirm the concepts implicit in [42-44]. That is, that a signal transduction cascade feeds through p19ARF and mdm2 to activate p53 in response to activation of oncogenes. Interestingly, [44] showed that the role of p19ARF in activation of p53 is restricted to activation by oncogenes and it is not required for activation by DNA damage. This implies that oncogenes activate p53 in a manner that is independent of any capacity that they have to cause DNA damage.
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De Stanchina, E.1
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Ferbeyre, G.5
Samuelson, A.V.6
Prives, C.7
Roussel, M.8
Sherr, C.J.9
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41
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0032145569
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Myc signalling via the ARF tumour suppressor regulates p53-dependent apoptosis and immortalisation
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of outstanding interest. See annotation to [40].
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Zindy F, Eischen CM, Randle DH, Kamijo T, Cleveland JL, Sherr CJ, Roussel MF. Myc signalling via the ARF tumour suppressor regulates p53-dependent apoptosis and immortalisation. of outstanding interest Genes Dev. 12:1998;2424-2433 See annotation to [40].
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Zindy, F.1
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Sherr, C.J.6
Roussel, M.F.7
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42
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ARF promotes MDM2 degradation and stabilises p53: ARF-INK4a locus deletion impairs both the RB and p53 tumour suppression pathways
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ARF and mdm2 might be responsible for stabilization of p53.
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ARF and mdm2 might be responsible for stabilization of p53.
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43
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The INK4a tumour suppressor gene product, p19ARF, interacts with MDM2 and neutralises MDM2's inhibition of p53
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of outstanding interest. See annotation to [42].
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Pomerantz J, Schreiber-Agus N, Liegeois NJ, Silverman A, Alland L, Chin L, Potes J, Chen K, Orlow I, Lee HW, et al. The INK4a tumour suppressor gene product, p19ARF, interacts with MDM2 and neutralises MDM2's inhibition of p53. of outstanding interest Cell. 92:1998;713-723 See annotation to [42].
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Kastan, M.B.1
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El-Deiry, W.S.3
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Walsh, W.V.6
Plunkett, B.S.7
Vogelstein, B.8
Fornace A.J., Jr.9
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47
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0029057336
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A single ataxia-telangiectasia gene with a product similar to PI-3 kinase
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Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S. A single ataxia-telangiectasia gene with a product similar to PI-3 kinase. Science. 268:1995;1749-1753.
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Savitsky, K.1
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Gilad, S.3
Rotman, G.4
Ziv, Y.5
Vanagaite, L.6
Tagle, D.A.7
Smith, S.8
Uziel, T.9
Sfez, S.10
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48
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0031435944
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DNA damage induces phosphorylation of the amino-terminus of p53
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of outstanding interest. This paper demonstrates that p53 becomes phosphorylated on Ser15 in response to ionizing or UV irradiation. Together with [49] it suggests that phosphorylation of p53 in response to DNA damage might inhibit degradation promoted by mdm2. This paper also shows that, at least in response to ionizing radiation, phosphorylation of Ser15 is partly dependent upon the ATM kinase.
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Siliciano JD, Canman CE, Taya Y, Sakaguchi K, Appella E, Kastan M. DNA damage induces phosphorylation of the amino-terminus of p53. of outstanding interest Genes Dev. 11:1997;3471-3481 This paper demonstrates that p53 becomes phosphorylated on Ser15 in response to ionizing or UV irradiation. Together with [49] it suggests that phosphorylation of p53 in response to DNA damage might inhibit degradation promoted by mdm2. This paper also shows that, at least in response to ionizing radiation, phosphorylation of Ser15 is partly dependent upon the ATM kinase.
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(1997)
Genes Dev
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Siliciano, J.D.1
Canman, C.E.2
Taya, Y.3
Sakaguchi, K.4
Appella, E.5
Kastan, M.6
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49
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0030667702
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DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2
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of outstanding interest. This paper demonstrates that phosphorylation of p53 on Ser15 by DNA-dependent protein kinase (DNA-PK), a kinase related to ATM, results in inhibition of mdm2 binding. Thus, phosphorylation at this site would be expected to both stabilize p53 and promote transactivation. Reference [48] suggests that ATM is required for efficient stabilization of p53, at least in response to ionizing radiation, and reference [50] suggests that DNA-PK is required for DNA-binding of and transcriptional activation by p53, but not for stabilization of p53.
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Shieh SY, Ikeda m, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. of outstanding interest Cell. 91:1997;325-334 This paper demonstrates that phosphorylation of p53 on Ser15 by DNA-dependent protein kinase (DNA-PK), a kinase related to ATM, results in inhibition of mdm2 binding. Thus, phosphorylation at this site would be expected to both stabilize p53 and promote transactivation. Reference [48] suggests that ATM is required for efficient stabilization of p53, at least in response to ionizing radiation, and reference [50] suggests that DNA-PK is required for DNA-binding of and transcriptional activation by p53, but not for stabilization of p53.
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(1997)
Cell
, vol.91
, pp. 325-334
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Shieh, S.Y.1
Ikeda, M.2
Taya, Y.3
Prives, C.4
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50
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0032514485
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DNA-dependent protein kinase acts upstream of p53 in response to DNA damage
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of outstanding interest. See annotation to [49].
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Woo RA, McLure KG, Lees-Miller SP, Rancourt DE, Lee PWK. DNA-dependent protein kinase acts upstream of p53 in response to DNA damage. of outstanding interest Nature. 394:1998;700-704 See annotation to [49].
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(1998)
Nature
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, pp. 700-704
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Woo, R.A.1
McLure, K.G.2
Lees-Miller, S.P.3
Rancourt, D.E.4
Lee, P.W.K.5
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51
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0031310665
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2/M progression
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2/M arrest. In proposing a role for 14.3.3 proteins in this checkpoint it is entirely consistent with the recent studies of others [52-54]; moreover, since 14.3.3 proteins have homologues in Schizosaccharomyces pombe in the guise of the checkpoint genes Rad24 and Rad25, it provides a point of convergence between yeast checkpoint genetics and a p53 dependent checkpoint.
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2/M arrest. In proposing a role for 14.3.3 proteins in this checkpoint it is entirely consistent with the recent studies of others [52-54]; moreover, since 14.3.3 proteins have homologues in Schizosaccharomyces pombe in the guise of the checkpoint genes Rad24 and Rad25, it provides a point of convergence between yeast checkpoint genetics and a p53 dependent checkpoint.
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(1997)
Mol Cell
, vol.1
, pp. 3-11
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Hermeking, H.1
Lengauer, C.2
Polyak, K.3
He, T.C.4
Zhang, L.5
Thiagalingam, S.6
Kinzler, K.7
Vogelstein, B.8
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52
-
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0030611095
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2 checkpoint control: Regulation of 14-3-3 protein binding by phosphorylation of cdc25C on serine-216
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of outstanding interest. of special interest. See annotation to [51].
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2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of cdc25C on serine-216. of special interest Science. 277:1997;1501-1505 See annotation to [51].
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(1997)
Science
, vol.277
, pp. 1501-1505
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Peng, C.Y.1
Graves, P.R.2
Thoma, R.S.3
Wu, Z.4
Shaw, A.S.5
Piwnica-Worms, H.6
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53
-
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0030867582
-
Conservation of the chk1 checkpoint pathway in mammals: Linkage of DNA damage to cdk regulation through cdc25
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of outstanding interest. of special interest. See annotation to [51].
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of outstanding interest Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, Elledge SJ. Conservation of the chk1 checkpoint pathway in mammals: linkage of DNA damage to cdk regulation through cdc25. of special interest Science. 277:1997;1497-1501 See annotation to [51].
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(1997)
Science
, vol.277
, pp. 1497-1501
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Sanchez, Y.1
Wong, C.2
Thoma, R.S.3
Richman, R.4
Wu, Z.5
Piwnica-Worms, H.6
Elledge, S.J.7
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54
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0030768948
-
Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase
-
of outstanding interest. of special interest. See annotation to [51].
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of outstanding interest Furnari B, Rhind N, Russell P. Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase. of special interest Science. 277:1997;1495-1497 See annotation to [51].
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Science
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Furnari, B.1
Rhind, N.2
Russell, P.3
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55
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0029664616
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Rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint
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Walworth NC, Bernards R. Rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint. Science. 271:1996;353-356.
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Science
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Walworth, N.C.1
Bernards, R.2
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56
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10244227923
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The ATR and ATM protein kinases associate with different sites along meiotically pairing chromosomes
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Keegan KS, Holtzman DA, Plug AW, Christenson ER, Brainerd EE, Flaggs G, Bentley NJ, Taylor EM, Meyn MS, Moss SB, et al. The ATR and ATM protein kinases associate with different sites along meiotically pairing chromosomes. Genes Dev. 10:1996;2423-2437.
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Keegan, K.S.1
Holtzman, D.A.2
Plug, A.W.3
Christenson, E.R.4
Brainerd, E.E.5
Flaggs, G.6
Bentley, N.J.7
Taylor, E.M.8
Meyn, M.S.9
Moss, S.B.10
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57
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0029127643
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ATM-related genes: What do they tell us about functions of the human gene?
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Zakian VA. ATM-related genes: what do they tell us about functions of the human gene? Cell. 82:1995;685-687.
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Cell
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Zakian, V.A.1
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58
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0030812331
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Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers
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of outstanding interest. These papers [58-61] reveal the existence of the p53-related family members p73 and p51. The existence of these proteins raises important questions regarding their functional similarities and differences with respect to p53.
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Kaghad M, Bonnet H, Yang A, Creancier L, Biscan J-C, Valent A, Minty A, Chalon P, Lelias J-M, Dumont X, et al. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. of outstanding interest Cell. 90:1997;809-819 These papers [58-61] reveal the existence of the p53-related family members p73 and p51. The existence of these proteins raises important questions regarding their functional similarities and differences with respect to p53.
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(1997)
Cell
, vol.90
, pp. 809-819
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Kaghad, M.1
Bonnet, H.2
Yang, A.3
Creancier, L.4
Biscan J-C5
Valent, A.6
Minty, A.7
Chalon, P.8
Lelias J-M9
Dumont, X.10
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59
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0031564954
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P73 is a human p53-related protein that can induce apoptosis
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of outstanding interest. See annotation to [58].
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Jost CA, Marin MC, Kaelin WG Jr. p73 is a human p53-related protein that can induce apoptosis. of outstanding interest Nature. 389:1997;191-194 See annotation to [58].
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(1997)
Nature
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, pp. 191-194
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Jost, C.A.1
Marin, M.C.2
Kaelin W.G., Jr.3
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60
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0031852337
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Cloning and functional analysis of human p51, which structurally and functionally resembles p53
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of outstanding interest. See annotation to [58].
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Osada M, Ohba M, Kawahara C, Ishioka C, Kanamaru R, Katoh I, Ikawa Y, Nimura Y, Nakagawara A, Obinata M, Ikawa S. Cloning and functional analysis of human p51, which structurally and functionally resembles p53. of outstanding interest Nat Med. 4:1998;839-843 See annotation to [58].
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Nat Med
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Osada, M.1
Ohba, M.2
Kawahara, C.3
Ishioka, C.4
Kanamaru, R.5
Katoh, I.6
Ikawa, Y.7
Nimura, Y.8
Nakagawara, A.9
Obinata, M.10
Ikawa, S.11
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61
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0031874340
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A new human p53 homologue
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of outstanding interest. See annotation to [58].
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Trink B, Okami K, Wu L, Sriuranpong V, Jen J, Sidransky D. A new human p53 homologue. of outstanding interest Nat Med. 4:1998;747-748 See annotation to [58].
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Nat Med
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Trink, B.1
Okami, K.2
Wu, L.3
Sriuranpong, V.4
Jen, J.5
Sidransky, D.6
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62
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0029993450
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Role of INK4a locus in tumour suppression and cell mortality
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Serrano M, Lee H-W, Chin L, Cordon-Cardo C, Beach D, DePinho RA. Role of INK4a locus in tumour suppression and cell mortality. Cell. 85:1996;27-37.
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Lee H-W2
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The spindle checkpoint
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Harwick KG. The spindle checkpoint. Trends Genet. 14:1998;1-4.
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Trends Genet
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Harwick, K.G.1
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64
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0032546360
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Mutations of mitotic checkpoint genes in human cancers
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of outstanding interest. These two papers [64,65] are the first to suggest that proteins in the mitotic spindle assembly checkpoint pathway are targets for functional inactivation in human cancer. As such, they further extend the concept of 'tumour suppression pathways' that was initially established through the study of pRB and p53.
-
Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JKV, Markowitz SD, Kinzler KW, Vogelstein B. Mutations of mitotic checkpoint genes in human cancers. of outstanding interest Nature. 392:1998;300-303 These two papers [64,65] are the first to suggest that proteins in the mitotic spindle assembly checkpoint pathway are targets for functional inactivation in human cancer. As such, they further extend the concept of 'tumour suppression pathways' that was initially established through the study of pRB and p53.
-
(1998)
Nature
, vol.392
, pp. 300-303
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-
Cahill, D.P.1
Lengauer, C.2
Yu, J.3
Riggins, G.J.4
Willson, J.K.V.5
Markowitz, S.D.6
Kinzler, K.W.7
Vogelstein, B.8
-
65
-
-
0032478547
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Human T cell leukemia virus type 1 oncoprotein tax targets the human mitotic checkpoint protein MAD1
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of outstanding interest. See annotation to [64].
-
Jin D-Y, Spencer F, Jeang K-T. Human T cell leukemia virus type 1 oncoprotein tax targets the human mitotic checkpoint protein MAD1. of outstanding interest Cell. 93:1998;81-91 See annotation to [64].
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(1998)
Cell
, vol.93
, pp. 81-91
-
-
Jin D-Y1
Spencer, F.2
Jeang K-T3
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66
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0030930366
-
A model for p53-induced apoptosis
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of outstanding interest. This paper describes a powerful technique (SAGE) for isolating differentially expressed mRNAs. Using this approach, the authors show that p53 activates the transcription of redox-related genes culminating in the generation of reactive oxygen species that can degrade mitochondria.
-
Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. A model for p53-induced apoptosis. of outstanding interest Nature. 389:1997;300-305 This paper describes a powerful technique (SAGE) for isolating differentially expressed mRNAs. Using this approach, the authors show that p53 activates the transcription of redox-related genes culminating in the generation of reactive oxygen species that can degrade mitochondria.
-
(1997)
Nature
, vol.389
, pp. 300-305
-
-
Polyak, K.1
Xia, Y.2
Zweier, J.L.3
Kinzler, K.W.4
Vogelstein, B.5
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