p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest.
10.1101/gad.8.1.9
Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
Abstract

Cell-cell contact and TGF-beta can arrest the cell cycle in G1. Mv1Lu mink epithelial cells arrested by either mechanism are incapable of assembling active complexes containing the G1 cyclin, cyclin E, and its catalytic subunit, Cdk2. These growth inhibitory signals block Cdk2 activation by raising the threshold level of cyclin E necessary to activate Cdk2. In arrested cells the threshold is set higher than physiological cyclin E levels and is determined by an inhibitor that binds to cyclin E-Cdk2 complexes. A 27-kD protein that binds to and prevents the activation of cyclin E-Cdk2 complexes can be purified from arrested cells but not from proliferating cells, using cyclin E-Cdk2 affinity chromatography. p27 is present in proliferating cells, but it is sequestered and unavailable to interact with cyclin E-Cdk2 complexes. Cyclin D2-Cdk4 complexes bind competitively to and down-regulate the activity of p27 and may thereby act in a pathway that reverses Cdk2 inhibition and enables G1 progression.

Bibliography

Polyak, K., Kato, J. Y., Solomon, M. J., Sherr, C. J., Massague, J., Roberts, J. M., & Koff, A. (1994). p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes & Development, 8(1), 9–22.

Authors 7
  1. K Polyak (first)
  2. J Y Kato (additional)
  3. M J Solomon (additional)
  4. C J Sherr (additional)
  5. J Massague (additional)
  6. J M Roberts (additional)
  7. A Koff (additional)
References 75 Referenced 1,481
  1. 10.1038/364824a0
  2. 10.1016/0092-8674(90)90261-C
  3. 10.1016/0076-6879(91)01013-R
  4. 10.1016/0092-8674(80)90524-3
  5. 10.1016/0092-8674(90)90503-7
  6. 10.1016/0092-8674(90)90191-G
  7. 10.1091/mbc.3.5.571
  8. 10.1016/0092-8674(93)90137-F
  9. 10.1126/science.1329201
  10. 10.1016/0092-8674(89)90414-5
  11. 10.1126/science.2173140
  12. 10.1002/j.1460-2075.1991.tb07808.x / EMBO J. / A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of the Xenopus Eg1 gene. (1991)
  13. 10.1073/pnas.89.7.2907
  14. 10.1016/0092-8674(90)90669-6
  15. 10.1016/0092-8674(93)90136-E
  16. 10.1016/0092-8674(93)90723-4
  17. 10.1016/0092-8674(91)90117-H
  18. 10.1002/j.1460-2075.1993.tb05980.x / EMBO J. / The MO15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (CDKs) through phosphorylation of Thr161 and its homologues. (1993)
  19. 10.1073/pnas.72.3.869
  20. 10.1126/science.2237430
  21. 10.1016/0092-8674(91)90293-8
  22. 10.1038/342039a0
  23. 10.1002/j.1460-2075.1991.tb04894.x / EMBO J. / Phosphorylation at Thr 167 is required for Schizosaccharomyces pombe p34CDC2 function. (1991)
  24. {'key': '2021111418115840000_8.1.9.24', 'first-page': '995', 'article-title': 'Cell cycle regulation of CDK2 activity by phosphorylation of Thr 160 and Tyr15.', 'volume': '11', 'year': '1992', 'journal-title': 'EMBO J.'} / EMBO J. / Cell cycle regulation of CDK2 activity by phosphorylation of Thr 160 and Tyr15. (1992)
  25. 10.1093/genetics/129.4.975 / Genetics / Twenty-five years of cell cycle genetics. (1991)
  26. 10.1126/science.2683079
  27. 10.1126/science.183.4120.46
  28. 10.1016/0092-8674(93)80048-J
  29. 10.1016/0092-8674(92)90249-C
  30. {'key': '2021111418115840000_8.1.9.30', 'first-page': '1185', 'article-title': 'Transforming growth factor β1 inhibition of p34cdc2 phosphorylation and histone H1 kinase activity is associated with G1/S-phase growth arrest.', 'volume': '11', 'year': '1991', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Transforming growth factor β1 inhibition of p34cdc2 phosphorylation and histone H1 kinase activity is associated with G1/S-phase growth arrest. (1991)
  31. 10.1016/0092-8674(81)90014-3
  32. 10.1016/0092-8674(92)90108-O
  33. Kato, J.Y. and Sherr. C.J. 1993. Inhibition of granulocyte differentiation by G1 cyclins D2 and D3, but not D1. Proc. Natl. Acad. Sci. (in press). (10.1073/pnas.90.24.11513)
  34. 10.1101/gad.7.3.331
  35. 10.1016/0092-8674(91)90044-Y
  36. 10.1126/science.1388288
  37. 10.1126/science.8475385
  38. 10.1002/j.1460-2075.1991.tb07951.x / EMBO J. / Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: Identification of major phosphorylation sites. (1991)
  39. 10.1016/0092-8674(91)90315-P
  40. 10.1016/0092-8674(90)90251-9
  41. 10.1016/0092-8674(91)90042-W
  42. 10.1016/0092-8674(81)90015-5
  43. {'key': '2021111418115840000_8.1.9.43', 'first-page': '1111', 'article-title': 'mik1 and weel cooperate in the inhibitory tyrosine phosphorylation of cdc2.', 'volume': '764', 'year': '1991', 'journal-title': 'Cell'} / Cell / mik1 and weel cooperate in the inhibitory tyrosine phosphorylation of cdc2. (1991)
  44. 10.1016/0092-8674(91)90101-4
  45. 10.1016/0092-8674(92)90360-O
  46. 10.1126/science.8421781
  47. 10.1038/344503a0
  48. 10.1126/science.8384376
  49. 10.1002/j.1460-2075.1992.tb05135.x / EMBO J. / Cyclin A is required at two points in the human cell cycle. (1992)
  50. 10.1083/jcb.121.1.101
  51. 10.1073/pnas.71.4.1286
  52. 10.1126/science.2683075
  53. 10.1073/pnas.88.3.1029
  54. 10.1016/0092-8674(93)90254-N
  55. 10.1002/j.1460-2075.1993.tb05981.x / EMBO J. / The cdc2-related protein p40 MO15 is the catalytic subunit of a protein kinase that can activate p33 CDK2 and p34 CDC2. (1993)
  56. 10.1101/gad.7.8.1559
  57. 10.1073/pnas.74.7.2869
  58. 10.1083/jcb.75.2.355
  59. 10.1073/pnas.89.7.2824
  60. 10.1038/356353a0
  61. 10.1016/0092-8674(93)90636-5 / Cell / Mammalian G1 cyclins. (1993)
  62. 10.1073/pnas.70.4.1263
  63. 10.1016/0092-8674(92)90153-4
  64. 10.1091/mbc.3.1.13
  65. 10.1002/j.1460-2075.1993.tb05982.x / EMBO J. / CAK, the p34 CDC2 activating kinase, contains a protein identical or closely related to p40 M015. (1993)
  66. 10.1038/355365a0
  67. {'key': '2021111418115840000_8.1.9.67', 'first-page': '3744', 'article-title': 'Full activation of p34 CDC28 histone H1 kinase activity is unable to promote entry into mitosis in checkpoint-arrested cells of the yeast Saccharomyces cerevisiae.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Full activation of p34 CDC28 histone H1 kinase activity is unable to promote entry into mitosis in checkpoint-arrested cells of the yeast Saccharomyces cerevisiae. (1993)
  68. {'key': '2021111418115840000_8.1.9.68', 'first-page': '555', 'article-title': 'Isolation of the human Cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase.', 'volume': '33', 'year': '1991', 'journal-title': 'Nature'} / Nature / Isolation of the human Cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. (1991)
  69. {'key': '2021111418115840000_8.1.9.69', 'first-page': '1593', 'article-title': 'The cdk2 kinase is required for the G1-to-S phase transition in mammalian cells.', 'volume': '8', 'year': '1993', 'journal-title': 'Oncogene'} / Oncogene / The cdk2 kinase is required for the G1-to-S phase transition in mammalian cells. (1993)
  70. 10.1038/363368a0
  71. 10.1126/science.3291120
  72. 10.1016/0092-8674(90)90361-H
  73. 10.1073/pnas.89.20.9910
  74. 10.1016/0092-8674(92)90518-H
  75. 10.1101/gad.7.8.1572
Dates
Type When
Created 18 years, 3 months ago (June 5, 2007, 5:15 p.m.)
Deposited 3 years, 9 months ago (Nov. 14, 2021, 9:13 p.m.)
Indexed 2 days, 11 hours ago (Sept. 3, 2025, 7:16 a.m.)
Issued 31 years, 8 months ago (Jan. 1, 1994)
Published 31 years, 8 months ago (Jan. 1, 1994)
Published Online 31 years, 8 months ago (Jan. 1, 1994)
Published Print 31 years, 8 months ago (Jan. 1, 1994)
Funders 0

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@article{Polyak_1994, title={p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest.}, volume={8}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.8.1.9}, DOI={10.1101/gad.8.1.9}, number={1}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Polyak, K and Kato, J Y and Solomon, M J and Sherr, C J and Massague, J and Roberts, J M and Koff, A}, year={1994}, month=jan, pages={9–22} }