Chk2 splice variants express a dominant-negative effect on the wild-type Chk2 kinase activity

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1803, Issue 3, 2010, Pages 386-395

  Berge, Elisabet Ognedal ^a   Staalesen, Vidar ^a   Straume, Anne Hege ^a   Lillehaug, Johan Richard ^a   Lønning, Per Eystein ^a,b  

^a UNIVERSITY OF BERGEN   (Norway)

^b HAUKELAND UNIVERSITY HOSPITAL   (Norway)

Author keywords

Breast cancer; Chk2; Splicing

Indexed keywords

CHECKPOINT KINASE 2; MESSENGER RNA; NUCLEAR PROTEIN;

ARTICLE; BREAST CARCINOMA; CONTROLLED STUDY; DIMERIZATION; ENZYME ACTIVITY; ENZYME ASSAY; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IMMUNOFLUORESCENCE; IMMUNOPRECIPITATION; PLASMID; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN INTERACTION; RNA SPLICING; WESTERN BLOTTING; WILD TYPE;

ALTERNATIVE SPLICING; BREAST NEOPLASMS; CELL CYCLE PROTEINS; CELL LINE, TUMOR; CELL NUCLEUS; DNA-BINDING PROTEINS; FEMALE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; PROTEIN ISOFORMS; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, QUATERNARY; PROTEIN-SERINE-THREONINE KINASES; SUBSTRATE SPECIFICITY; TUMOR SUPPRESSOR PROTEINS;

EID: 77249090660     PISSN: 01674889     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2010.01.005     Document Type: Article

References (58)

1. Black D.L. Mechanisms of alternative pre-messenger RNA splicing. Annu. Rev. Biochem. 72 (2003) 291-336
2. Matlin A.J., Clark F., and Smith C.W. Understanding alternative splicing: towards a cellular code. Nat. Rev., Mol. Cell Biol. 6 (2005) 386-398
3. Srebrow A., and Kornblihtt A.R. The connection between splicing and cancer. J. Cell Sci. 119 (2006) 2635-2641
4. Caceres J.F., and Kornblihtt A.R. Alternative splicing: multiple control mechanisms and involvement in human disease. Trends Genet. 18 (2002) 186-193
5. Faustino N.A., and Cooper T.A. Pre-mRNA splicing and human disease. Genes Dev. 17 (2003) 419-437
6. Kalnina Z., Zayakin P., Silina K., and Line A. Alterations of pre-mRNA splicing in cancer. Genes Chromosomes Cancer 42 (2005) 342-357
7. Pajares M.J., Ezponda T., Catena R., Calvo A., Pio R., and Montuenga L.M. Alternative splicing: an emerging topic in molecular and clinical oncology. Lancet Oncol. 8 (2007) 349-357
8. Venables J.P. Aberrant and alternative splicing in cancer. Cancer Res. 64 (2004) 7647-7654
9. Narla G., Difeo A., Reeves H.L., Schaid D.J., Hirshfeld J., Hod E., Katz A., Isaacs W.B., Hebbring S., Komiya A., McDonnell S.K., Wiley K.E., Jacobsen S.J., Isaacs S.D., Walsh P.C., Zheng S.L., Chang B.L., Friedrichsen D.M., Stanford J.L., Ostrander E.A., Chinnaiyan A.M., Rubin M.A., Xu J., Thibodeau S.N., Friedman S.L., and Martignetti J.A. A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk. Cancer Res. 65 (2005) 1213-1222
10. Ahn J.Y., Schwarz J.K., Piwnica-Worms H., and Canman C.E. Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res. 60 (2000) 5934-5936
11. Xu X., Tsvetkov L.M., and Stern D.F. Chk2 activation and phosphorylation-dependent oligomerization. Mol. Cell. Biol. 22 (2002) 4419-4432
12. Lee C.H., and Chung J.H. The hCds1 (Chk2)-FHA domain is essential for a chain of phosphorylation events on hCds1 that is induced by ionizing radiation. J. Biol. Chem. 276 (2001) 30537-30541
13. Schwarz J.K., Lovly C.M., and Piwnica-Worms H. Regulation of the Chk2 protein kinase by oligomerization-mediated cis- and trans-phosphorylation. Mol. Cancer Res. 1 (2003) 598-609
14. Falck J., Mailand N., Syljuasen R.G., Bartek J., and Lukas J. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 410 (2001) 842-847
15. Blasina A., de Weyer I.V., Laus M.C., Luyten W.H., Parker A.E., and McGowan C.H. A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase. Curr. Biol. 9 (1999) 1-10
16. Matsuoka S., Huang M., and Elledge S.J. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282 (1998) 1893-1897
17. Shieh S.Y., Ahn J., Tamai K., Taya Y., and Prives C. The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev. 14 (2000) 289-300
18. Chehab N.H., Malikzay A., Stavridi E.S., and Halazonetis T.D. Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 13777-13782
19. Chehab N.H., Malikzay A., Appel M., and Halazonetis T.D. Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes Dev. 14 (2000) 278-288
20. Staalesen V., Falck J., Geisler S., Bartkova J., Borresen-Dale A.L., Lukas J., Lillehaug J.R., Bartek J., and Lonning P.E. Alternative splicing and mutation status of CHEK2 in stage III breast cancer. Oncogene 23 (2004) 8535-8544
21. Chrisanthar R., Knappskog S., Lokkevik E., Anker G., Ostenstad B., Lundgren S., Berge E.O., Risberg T., Mjaaland I., Maehle L., Engebretsen L.F., Lillehaug J.R., and Lonning P.E. CHEK2 mutations affecting kinase activity together with mutations in TP53 indicate a functional pathway associated with resistance to epirubicin in primary breast cancer. PLoS ONE 3 (2008) e3062
22. Geisler S., Lonning P.E., Aas T., Johnsen H., Fluge O., Haugen D.F., Lillehaug J.R., Akslen L.A., and Borresen-Dale A.L. Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer. Cancer Res. 61 (2001) 2505-2512
23. Geisler S., Borresen-Dale A.L., Johnsen H., Aas T., Geisler J., Akslen L.A., Anker G., and Lonning P.E. TP53 gene mutations predict the response to neoadjuvant treatment with 5-fluorouracil and mitomycin in locally advanced breast cancer. Clin. Cancer Res. 9 (2003) 5582-5588
24. Jallepalli P.V., Lengauer C., Vogelstein B., and Bunz F. The Chk2 tumor suppressor is not required for p53 responses in human cancer cells. J. Biol. Chem. 278 (2003) 20475-20479
25. Arnesen T., Anderson D., Baldersheim C., Lanotte M., Varhaug J.E., and Lillehaug J.R. Identification and characterization of the human ARD1-NATH protein acetyltransferase complex. Biochem. J. 386 (2005) 433-443
26. Starheim K.K., Arnesen T., Gromyko D., Ryningen A., Varhaug J.E., and Lillehaug J.R. Identification of the human N(alpha)-acetyltransferase complex B (hNatB): a complex important for cell-cycle progression. Biochem. J. 415 (2008) 325-331
27. Fluge O., Haugen D.R., Akslen L.A., Marstad A., Santoro M., Fusco A., Varhaug J.E., and Lillehaug J.R. Expression and alternative splicing of c-ret RNA in papillary thyroid carcinomas. Oncogene 20 (2001) 885-892
28. Falck J., Lukas C., Protopopova M., Lukas J., Selivanova G., and Bartek J. Functional impact of concomitant versus alternative defects in the Chk2-p53 tumour suppressor pathway. Oncogene 20 (2001) 5503-5510
29. Zannini L., Lecis D., Lisanti S., Benetti R., Buscemi G., Schneider C., and Delia D. Karyopherin-alpha2 protein interacts with Chk2 and contributes to its nuclear import. J. Biol. Chem. 278 (2003) 42346-42351
30. Wu X., and Chen J. Autophosphorylation of checkpoint kinase 2 at serine 516 is required for radiation-induced apoptosis. J. Biol. Chem. 278 (2003) 36163-36168
31. Ahn J.Y., Li X., Davis H.L., and Canman C.E. Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain. J. Biol. Chem. 277 (2002) 19389-19395
32. Oliver A.W., Paul A., Boxall K.J., Barrie S.E., Aherne G.W., Garrett M.D., Mittnacht S., and Pearl L.H. Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange. EMBO J. 25 (2006) 3179-3190
33. Bell D.W., Varley J.M., Szydlo T.E., Kang D.H., Wahrer D.C., Shannon K.E., Lubratovich M., Verselis S.J., Isselbacher K.J., Fraumeni J.F., Birch J.M., Li F.P., Garber J.E., and Haber D.A. Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286 (1999) 2528-2531
34. Bougeard G., Limacher J.M., Martin C., Charbonnier F., Killian A., Delattre O., Longy M., Jonveaux P., Fricker J.P., Stoppa-Lyonnet D., Flaman J.M., and Frebourg T. Detection of 11 germline inactivating TP53 mutations and absence of TP63 and HCHK2 mutations in 17 French families with Li-Fraumeni or Li-Fraumeni-like syndrome. J. Med. Genet. 38 (2001) 253-257
35. Evans D.G., Birch J.M., and Narod S.A. Is CHEK2 a cause of the Li-Fraumeni syndrome?. J. Med. Genet. 45 (2008) 63-64
36. Evans D.G., Wu C.L., and Birch J.M. BRCA2: a cause of Li-Fraumeni-like syndrome. J. Med. Genet. 45 (2008) 62-63
37. Siddiqui R., Onel K., Facio F., Nafa K., Diaz L.R., Kauff N., Huang H., Robson M., Ellis N., and Offit K. The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds. Fam. Cancer 4 (2005) 177-181
38. Sodha N., Houlston R.S., Bullock S., Yuille M.A., Chu C., Turner G., and Eeles R.A. Increasing evidence that germline mutations in CHEK2 do not cause Li-Fraumeni syndrome. Hum. Mutat. 20 (2002) 460-462
39. Sodha N., Williams R., Mangion J., Bullock S.L., Yuille M.R., and Eeles R.A. Screening hCHK2 for mutations. Science 289 (2000) 359
40. Vahteristo P., Tamminen A., Karvinen P., Eerola H., Eklund C., Aaltonen L.A., Blomqvist C., Aittomaki K., and Nevanlinna H. p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. Cancer Res. 61 (2001) 5718-5722
41. Nevanlinna H., and Bartek J. The CHEK2 gene and inherited breast cancer susceptibility. Oncogene 25 (2006) 5912-5919
42. Weischer M., Bojesen S.E., Ellervik C., Tybjaerg-Hansen A., and Nordestgaard B.G. CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26, 000 patient cases and 27, 000 controls. J. Clin. Oncol. 26 (2008) 542-548
43. Kilpivaara O., Vahteristo P., Falck J., Syrjakoski K., Eerola H., Easton D., Bartkova J., Lukas J., Heikkila P., Aittomaki K., Holli K., Blomqvist C., Kallioniemi O.P., Bartek J., and Nevanlinna H. CHEK2 variant I157T may be associated with increased breast cancer risk. Int. J. Cancer 111 (2004) 543-547
44. Bogdanova N., Enssen-Dubrowinskaja N., Feshchenko S., Lazjuk G.I., Rogov Y.I., Dammann O., Bremer M., Karstens J.H., Sohn C., and Dork T. Association of two mutations in the CHEK2 gene with breast cancer. Int. J. Cancer 116 (2005) 263-266
45. Cybulski C., Gorski B., Huzarski T., Masojc B., Mierzejewski M., Debniak T., Teodorczyk U., Byrski T., Gronwald J., Matyjasik J., Zlowocka E., Lenner M., Grabowska E., Nej K., Castaneda J., Medrek K., Szymanska A., Szymanska J., Kurzawski G., Suchy J., Oszurek O., Witek A., Narod S.A., and Lubinski J. CHEK2 is a multiorgan cancer susceptibility gene. Am. J. Hum. Genet. 75 (2004) 1131-1135
46. Cybulski C., Wokolorczyk D., Huzarski T., Byrski T., Gronwald J., Gorski B., Debniak T., Masojc B., Jakubowska A., van de Wetering T., Narod S.A., and Lubinski J. A deletion in CHEK2 of 5, 395 bp predisposes to breast cancer in Poland. Breast Cancer Res. Treat. 102 (2007) 119-122
47. Walsh T., Casadei S., Coats K.H., Swisher E., Stray S.M., Higgins J., Roach K.C., Mandell J., Lee M.K., Ciernikova S., Foretova L., Soucek P., and King M.C. Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295 (2006) 1379-1388
48. Shaag A., Walsh T., Renbaum P., Kirchhoff T., Nafa K., Shiovitz S., Mandell J.B., Welcsh P., Lee M.K., Ellis N., Offit K., Levy-Lahad E., and King M.C. Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population. Hum. Mol. Genet. 14 (2005) 555-563
49. Sullivan A., Yuille M., Repellin C., Reddy A., Reelfs O., Bell A., Dunne B., Gusterson B.A., Osin P., Farrell P.J., Yulug I., Evans A., Ozcelik T., Gasco M., and Crook T. Concomitant inactivation of p53 and Chk2 in breast cancer. Oncogene 21 (2002) 1316-1324
50. Williams L.H., Choong D., Johnson S.A., and Campbell I.G. Genetic and epigenetic analysis of CHEK2 in sporadic breast, colon, and ovarian cancers. Clin. Cancer Res. 12 (2006) 6967-6972
51. Huang T.S., Myklebust L.M., Kjarland E., Gjertsen B.T., Pendino F., Bruserud O., Doskeland S.O., and Lillehaug J.R. LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human acute myelogenic leukemia patients and protects leukemia cells from apoptosis in vitro. Mol. Cancer 6 (2007) 31
52. Yang Y., Hu W., Feng S., Ma J., and Wu M. RIP3 beta and RIP3 gamma, two novel splice variants of receptor-interacting protein 3 (RIP3), downregulate RIP3-induced apoptosis. Biochem. Biophys. Res. Commun. 332 (2005) 181-187
53. van Doorn R., Dijkman R., Vermeer M.H., Starink T.M., Willemze R., and Tensen C.P. A novel splice variant of the Fas gene in patients with cutaneous T-cell lymphoma. Cancer Res. 62 (2002) 5389-5392
54. Bartek J., Falck J., and Lukas J. CHK2 kinase-a busy messenger. Nat. Rev., Mol. Cell Biol. 2 (2001) 877-886
55. Ahn J., and Prives C. Checkpoint kinase 2 (Chk2) monomers or dimers phosphorylate Cdc25C after DNA damage regardless of threonine 68 phosphorylation. J. Biol. Chem. 277 (2002) 48418-48426
56. Miller C.W., Ikezoe T., Krug U., Hofmann W.K., Tavor S., Vegesna V., Tsukasaki K., Takeuchi S., and Koeffler H.P. Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors. Genes Chromosomes Cancer 33 (2002) 17-21
57. Ingvarsson S., Sigbjornsdottir B.I., Huiping C., Hafsteinsdottir S.H., Ragnarsson G., Barkardottir R.B., Arason A., Egilsson V., and Bergthorsson J.T. Mutation analysis of the CHK2 gene in breast carcinoma and other cancers. Breast Cancer Res. 4 (2002) R4
58. Bartek J., and Lukas J. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cells 3 (2003) 421-429