The nucleolus: The magician's hat for cell cycle tricks

Current Opinion in Cell Biology

Volumn 12, Issue 3, 2000, Pages 372-377

  Visintin, Rosella ^a   Amon, Angelika ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RIBOSOME RNA;

CELL CYCLE; NONHUMAN; NUCLEOLUS; ONCOGENE; PACHYTENE; PRIORITY JOURNAL; PROTEIN RESTRICTION; REVIEW; YEAST;

EID: 0034098784     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-0674(00)00102-2     Document Type: Review

References (57)

1. Montgomery T.H. Comparative cytological studies, with special regard to the morphology of the nucleolus. J Morphol. 15:1898;265-582.
2. Franke W.W. Matthias Jacob Schleiden and the definition of the cell nucleus. Eur J Cell Biol. 47:1988;145-156.
3. Gerbi S.A. The nucleolus: then and now. Chromosoma. 105:1997;385-387.
4. Pederson T. The plurifunctional nucleolus. Nucleic Acid Res. 26:1998;3871-3876.
5. Elledge S.J. Cell cycle checkpoints: preventing an identity crisis. Science. 274:1996;1664-1672.
6. Morgan D.O. Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu Rev Cell Dev Biol. 13:1997;261-291.
7. Bai C., Sen P., Hofmann K., Ma L., Goebl M., Harper J.W., Elledge S.J. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 86:1996;263-274.
8. Feldman R.M.R., Correll C.C., Kaplan K.B., Deshaies R.J. A complex of Cdc4p, Skp1p, and Cdc53p/Cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell. 91:1997;221-230.
9. Skowyra D., Craig K.L., Tyers M., Elledge S.J., Harper J.W. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell. 91:1997;209-219.
10. Kamura T., Koepp D.M., Conrad M.N., Skowyra D., Moreland R.J., Iliopoulos O., Lane W.S., Kaelin W.G. Jr., Elledge S.J., Conaway R.C.et al. Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science. 284:1999;657-661.
11. Ohta T., Michel J.J., Schottelius A.J., Xiong Y. ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Mol Cell. 3:1999;535-541.
12. Seol J.H., Feldman R.M., Zachariae W., Shevchenko A., Correll C.C., Lyapina S., Chi Y., Galova M., Claypool J., Sandmeyer S.et al. Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34. Genes Dev. 13:1999;1614-1626.
13. Tan P., Fuchs S.Y., Chen A., Wu K., Gomez C., Ronai Z., Pan Z.Q. Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of IκBα Mol Cell. 3:1999;527-533.
14. King R.W., Peters J.M., Tugendreich S., Rolfe M., Hieter P., Kirschner M.W. A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell. 81:1995;279-288.
15. Sudakin V., Ganoth D., Dahan A., Heller H., Hershko J., Luca F.C., Ruderman J.V., Hershko A. The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol Biol Cell. 6:1995;185-197.
16. Irniger S., Piatti S., Michaelis C., Nasmyth K. Genes involved in sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast. Cell. 81:1995;269-278.
17. Cohen-Fix O., Peters J.M., Kirschner M.W., Koshland D. Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p. Genes Dev. 10:1996;3081-3093.
18. Surana U., Amon A., Dowzer C., McGrew J., Byers B., Nasmyth K. Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. EMBO J. 12:1993;1969-1978.
19. Visintin R., Craig K., Hwang E.S., Prinz S., Tyers M., Amon A. The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. Mol Cell. 2:1998;709-718. The authors show that the phosphatase Cdc14 triggers mitotic exit by three parallel mechanisms, each of which inhibits CDK activity. Cdc14 dephosphorylates Sic1, a CDK inhibitor, causing its stabilization. By dephosphorylating Swi5, a transcription factor for SIC1, Cdc14 induces SIC1 transcription. Dephosphorylation of Cdh1 by Cdc14 induces degradation of mitotic cyclins. Feedback between these pathways may lead to precipitous collapse of mitotic CDK activity and help to coordinate exit from mitosis.
20. 1, or in late mitosis due to the cdc14-1 mutation, is more responsive to Cdh1 than APC isolated from other stages of the cell cycle. Jaspersen et al. also show that Cdh1 is phosphorylated in vivo at multiple CDK consensus sites during cell-cycle stages when the activity of the cyclin-dependent kinase Cdc28 is high and the APC activity is low. Purified Cdh1 was phosphorylated in vitro at these sites by purified Cdc28-cyclin complexes, and phosphorylation abolished the ability of Cdh1 to activate the APC in vitro. The phosphatase Cdc14, known to be required for APC activation in vivo, was able to reverse the effects of Cdc28 by catalyzing Hct1 dephosphorylation and activation.
21. 1 through anaphase, RENT localizes to the nucleolus, and Cdc14 activity is inhibited by Cfi1/Net1. In late anaphase, Cdc14 dissociates from RENT and disperses throughout the cell in a TEM1-dependent manner, ultimately triggering mitotic exit.
22. Straight A.F., Shou W., Dowd G.J., Turck C.W., Deshaies R.J., Johnson A.D., Moazed D. Net1, a Sir2-associated nucleolar protein required for rDNA silencing and nucleolar integrity. Cell. 97:1999;245-256. Straight et al. show that Sir2, component of a nucleolar complex designated RENT, mediates gene silencing and the repression of recombination at the rDNA repeats in budding yeast. Cfi1/Net1, a core subunit of this complex, preferentially cross-links to the rDNA repeats, but not to silent DNA regions near telomeres or to active genes, and it tethers the RENT complex to rDNA. CFI1/NET1 is required for rDNA silencing and nucleolar integrity. During interphase, Cfi1/Net1 and Sir2 colocalize to a subdomain within the nucleous, but at the end of mitosis a fraction of Sir2 leaves the nucleolus and disperses as foci throughout the nucleus, suggesting that the structure of rDNA-silent chromatin changes during the cell cycle. These results suggest that a protein complex shown to regulate exit from mitosis is also involved in gene silencing.
23. 2 and mitosis, but spreads throughout the nucleus and cytoplasm during anaphase. A two-hybrid screen identified Cfi1/Net1 as the protein responsible for anchoring Cdc14 in the nucleolus. In cells lacking CFI1/NET1, Cdc14 is present in both the nucleus and cytoplasm throughout the cell cycle and cells exit mitosis prematurely. Furthermore, overexpression of CFI1/NET1 leads to Cfi1/Net1 protein and Cdc14 being present throughout the cell, indicating that Cfi1/Net1 determines the localization of Cdc14. Remarkably, these cells fail to exit mitosis suggesting that Cfi1/Net1 inhibits Cdc14 not only by sequestering it in the nucleolus but by Cfi1/Net1 acting as a catalytic inhibitor of Cdc14. A highly conserved signaling cascade, critical for the exit from mitosis, is required for the release of Cdc14 during anaphase.
24. Arf did not affect Mdm2 binding but prevented Mdm2 from inactivating p53.
25. ••].
26. San-Segundo P.A., Roeder G.S. Pch2 links chromatin silencing to meiotic checkpoint control. Cell. 97:1999;313-324. A hunt for mutants defective in the pachytene checkpoint identified the meiosis-specific gene PCH2. Cells defective in PCH2 fail to arrest in pachytene in response to defects in chromosome synapsis brought about by zip1, zip2 mutants, which are defective in synapsis, or dmc1 mutants, which are defective in recombination. Most of the Pch2 protein is localized in the nucleolus, where it represses meiotic interhomolog recombination in the rDNA region, perhaps by excluding the synaptonemal complex component Hop1 from this DNA region. Nucleolar localization of Pch2 depends on the silencing factor Sir2, and deletion of SIR2 also bypasses the zip1 pachytene arrest. Under certain circumstances, Sir3-dependent localization of Pch2 to telomeres also provides checkpoint function. These findings link the nucleolus, chromatin silencing, and the pachytene checkpoint.
27. Wan J., Xu H., Grunstein M. CDC14 of Saccharomyces cerevisiae. Cloning, sequence analysis, and transcription during the cell cycle. J Biol Chem. 267:1992;11274-11280.
28. Morgan D.O. Regulation of the APC and the exit from mitosis. Nat Cell Biol. 1:1999;E47-E53.
29. Weinert T. DNA damage checkpoints update: getting molecular. Curr Opin Genet Dev. 8:1998;185-193.
30. Giaccia A.J., Kastan M.B. The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev. 12:1998;2973-2983.
31. Prives C. Signaling to p53: breaking the MDM2-p53 circuit. Cell. 95:1998;5-8.
32. Shieh S.Y., Ikeda M., Taya Y., Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell. 91:1997;325-334.
33. Siliciano J.D., Canman C.E., Taya Y., Sakaguchi K., Appella E., Kastan M.B. DNA damage induces phosphorylation of the amino terminus of p53. Genes Dev. 11:1997;3471-3481.
34. Momand J., Zambetti G.P., Olson D.C., George D., Levine A.J. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell. 69:1992;1237-1245.
35. Oliner J.D., Pietenpol J.A., Thiagalingam S., Gyuris J., Kinzler K.W., Vogelstein B. Oncoprotein MDM2 conceals the activation domain of tumor suppressor p53. Nature. 362:1993;857-860.
36. Roth J., Dobbelstein M., Freedman D.A., Shenk T., Levine A.J. Nucleo-cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein. EMBO J. 17:1998;554-564.
37. Freedman D.A., Levine A.J. Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol Cell Biol. 18:1998;7288-7293.
38. Honda R., Tanaka H., Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420:1997;25-27.
39. Arf acts primarily on the level of Mdm2 rather than p53.
40. Arf and Mdm2, respectively.
41. Arf modulates p53-dependent function through an additional mechanism.
42. Arf in an independent pathway upstream of p53 and imply that the human CDKN2A locus encodes two proteins that are involved in tumor suppression.
43. Guddat U., Bakken A.H., Pieler T. Protein-mediated nuclear export of RNA: 5S rRNA containing small RNPs in xenopus oocytes. Cell. 60:1990;619-628.
44. Fridell R.A., Fischer U., Luhrmann R., Meyer B.E., Meinkoth J.L., Malim M.H., Cullen B.R. Amphibian transcription factor IIIA proteins contain a sequence element functionally equivalent to the nuclear export signal of human immunodeficiency virus type 1 Rev. Proc Natl Acad Sci USA. 93:1996;2936-2940.
45. Marechal V., Elenbaas B., Piette J., Nicolas J.C., Levine A.J. The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes. Mol Cell Biol. 14:1994;7414-7420.
46. Elenbaas B., Dobbelstein M., Roth J., Shenk T., Levine A.J. The MDM2 oncoprotein binds specifically to RNA through its RING finger domain. Mol Med. 2:1996;439-451.
47. Arf with a functional alteration.
48. Kleckner N. Meiosis: how could it work? Proc Natl Acad Sci USA. 93:1996;8167-8174.
49. Roeder G.S. Meiotic chromosomes: it takes two to tango. Genes Dev. 11:1997;2600-2621.
50. Bishop D.K., Park D., Xu L., Kleckner N. DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression. Cell. 69:1992;439-456.
51. Sym M., Engebrecht J.A., Roeder G.S. ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis. Cell. 72:1993;365-378.
52. McKee A.H., Kleckner N. Mutations in Saccharomyces cerevisiae that block meiotic prophase chromosome metabolism and confer cell cycle arrest at pachytene identify two new meiosis-specific genes SAE1 and SAE3. Genetics. 146:1997;817-834.
53. Chua P.R., Roeder G.S. Zip2, a meiosis-specific protein required for the initiation of chromosome synapsis. Cell. 93:1998;349-359.
54. Leu J.Y., Chua P.R., Roeder G.S. The meiosis-specific Hop2 protein of S. cerevisiae ensures synapsis between homologous chromosomes. Cell. 94:1998;375-386.
55. Tung K.S., Roeder G.S. Meiotic chromosome morphology and behavior in zip1 mutants of Saccharomyces cerevisiae. Genetics. 149:1998;817-832.
56. Lydall D., Nikolsky Y., Bishop D.K., Weinert T. A meiotic recombination checkpoint controlled by mitotic checkpoint genes. Nature. 383:1996;840-843.
57. Granot D., Snyder M. Segregation of the nucleolus during mitosis in budding and fission yeast. Cell Motil Cytoskeleton. 20:1991;47-54.