![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Research Papers
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Abstract
G1 progression in mammalian cells requires the activity of the cyclin D-dependent kinases Cdk4 and/or Cdk6 and the cyclin E-dependent kinase Cdk2. Proliferating Mv1Lu mink lung epithelial cells and human keratinocytes contain high levels of the universal Cdk inhibitor p27Kip1 distributed in complexes with Cdk2, Cdk4, and Cdk6. Addition of the antimitogenic cytokine transforming growth factor-beta (TGF-beta) elevates expression of the Cdk4/6-specific inhibitor p15Ink4B and induces the release of p27 from Cdk4 and Cdk6. In Mv1Lu cells, this release of p27 coincides with increased binding of p27 to Cdk2. Recombinant p15 inhibits p27 binding to Cdk4 in vitro, and p15 overexpression induces the transfer of p27 from Cdk4 to Cdk2 in vivo, suggesting that the release of Cdk4-bound p27 in TGF-beta-treated cells is caused by the surge in p15 levels. In keratinocytes, TGF-beta increases not only p15 but also p21Cip1, which binds to Cdk2. These events correlate with Cdk2 inhibition and cell cycle arrest and occur without a loss of G1 Cdk components. The results suggest that TGF-beta induces G1 arrest in these two epithelial cell types by inhibiting various cyclin-Cdk kinases through the cooperative action of an Ink4 Cdk inhibitor and a Cip/Kip Cdk inhibitor. Subsequent to cell cycle arrest, Cdk2 and Cdk4 levels decline as part of a second set of events that may represent a program of cell adaptation to the quiescent state.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Nakamura, H. Sakaue, A. Nishizawa, Y. Matsuki, H. Gomi, E. Watanabe, R. Hiramatsua, M. Tamamori-Adachi, S. Kitajima, T. Noda, et al. PDK1 Regulates Cell Proliferation and Cell Cycle Progression through Control of Cyclin D1 and p27Kip1 Expression J. Biol. Chem., June 20, 2008; 283(25): 17702 - 17711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, S. El-Naggar, D. S. Darling, Y. Higashi, and D. C. Dean Zeb1 links epithelial-mesenchymal transition and cellular senescence Development, February 1, 2008; 135(3): 579 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. James, A. Ray, D. Leznova, and S. W. Blain Differential Modification of p27Kip1 Controls Its Cyclin D-cdk4 Inhibitory Activity Mol. Cell. Biol., January 1, 2008; 28(1): 498 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Roy, S. Khanna, T. Rink, J. Radtke, W. T. Williams, S. Biswas, R. Schnitt, A. R. Strauch, and C. K. Sen p21waf1/cip1/sdi1 as a Central Regulator of Inducible Smooth Muscle Actin Expression and Differentiation of Cardiac Fibroblasts to Myofibroblasts Mol. Biol. Cell, December 1, 2007; 18(12): 4837 - 4846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lwin, L. A. Hazlehurst, S. Dessureault, R. Lai, W. Bai, E. Sotomayor, L. C. Moscinski, W. S. Dalton, and J. Tao Cell adhesion induces p27Kip1-associated cell-cycle arrest through down-regulation of the SCFSkp2 ubiquitin ligase pathway in mantle-cell and other non-Hodgkin B-cell lymphomas Blood, September 1, 2007; 110(5): 1631 - 1638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Landis, N. E. Brown, G. L. Baker, A. Shifrin, M. Das, Y. Geng, P. Sicinski, and P. W. Hinds The LxCxE pRb Interaction Domain of Cyclin D1 Is Dispensable for Murine Development Cancer Res., August 15, 2007; 67(16): 7613 - 7620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Barendrecht, A. C. M. Mulders, H. van der Poel, M. J. B. van den Hoff, M. Schmidt, and M. C. Michel Role of Transforming Growth Factor beta in Rat Bladder Smooth Muscle Cell Proliferation J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 117 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Susaki, K. Nakayama, and K. I. Nakayama Cyclin D2 Translocates p27 out of the Nucleus and Promotes Its Degradation at the G0-G1 Transition Mol. Cell. Biol., July 1, 2007; 27(13): 4626 - 4640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Liu, G. Wu, W. Li, D. Lobur, and Y. Wan Cdh1-Anaphase-Promoting Complex Targets Skp2 for Destruction in Transforming Growth Factor {beta}-Induced Growth Inhibition Mol. Cell. Biol., April 15, 2007; 27(8): 2967 - 2979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wu, S. Glickstein, W. Liu, T. Fujita, W. Li, Q. Yang, R. Duvoisin, and Y. Wan The Anaphase-promoting Complex Coordinates Initiation of Lens Differentiation Mol. Biol. Cell, March 1, 2007; 18(3): 1018 - 1029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Duan, Y.-Y. Liang, X.-H. Feng, and X. Lin Protein Serine/Threonine Phosphatase PPM1A Dephosphorylates Smad1 in the Bone Morphogenetic Protein Signaling Pathway J. Biol. Chem., December 1, 2006; 281(48): 36526 - 36532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kikuchi, C. Zhu, T. Senoo, Y. Obara, and N. C. Joyce p27kip1 siRNA Induces Proliferation in Corneal Endothelial Cells from Young but Not Older Donors Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4803 - 4809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Enomoto, T. Mimura, D. L. Harris, and N. C. Joyce Age differences in cyclin-dependent kinase inhibitor expression and rb hyperphosphorylation in human corneal endothelial cells. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4330 - 4340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ao, K. Williams, N. A. Bhowmick, and S. W. Hayward Transforming Growth Factor-{beta} Promotes Invasion in Tumorigenic but not in Nontumorigenic Human Prostatic Epithelial Cells Cancer Res., August 15, 2006; 66(16): 8007 - 8016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Teng, A.-N. Sun, X.-C. Pan, G. Yang, L.-L. Yang, M.-R. Wang, and X. Yang Synergistic Function of Smad4 and PTEN in Suppressing Forestomach Squamous Cell Carcinoma in the Mouse. Cancer Res., July 15, 2006; 66(14): 6972 - 6981. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bockstaele, H. Kooken, F. Libert, S. Paternot, J. E. Dumont, Y. de Launoit, P. P. Roger, and K. Coulonval Regulated Activating Thr172 Phosphorylation of Cyclin-Dependent Kinase 4(CDK4): Its Relationship with Cyclins and CDK "Inhibitors". Mol. Cell. Biol., July 1, 2006; 26(13): 5070 - 5085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Kim, J. Rowe, H. Fujii, R. Jones, B. Schmierer, B.-W. Kong, K. Kuchler, D. Foster, D. Ish-Horowicz, and G. Peters Upregulation of chicken p15INK4b at senescence and in the developing brain J. Cell Sci., June 15, 2006; 119(12): 2435 - 2443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Natarajan, J. D. Omobono II, Z. Guo, S. Hopkinson, A. J.F. Lazar, T. Brenn, J. C. Jones, and J. G. Rheinwald A Keratinocyte Hypermotility/Growth-Arrest Response Involving Laminin 5 and p16INK4A Activated in Wound Healing and Senescence Am. J. Pathol., June 1, 2006; 168(6): 1821 - 1837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Cucoranu, R. Clempus, A. Dikalova, P. J. Phelan, S. Ariyan, S. Dikalov, and D. Sorescu NAD(P)H Oxidase 4 Mediates Transforming Growth Factor-{beta}1-Induced Differentiation of Cardiac Fibroblasts Into Myofibroblasts Circ. Res., October 28, 2005; 97(9): 900 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Pasche, T. J. Knobloch, Y. Bian, J. Liu, S. Phukan, D. Rosman, V. Kaklamani, L. Baddi, F. S. Siddiqui, W. Frankel, et al. Somatic Acquisition and Signaling of TGFBR1*6A in Cancer JAMA, October 5, 2005; 294(13): 1634 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yang, C. Mao, Y. Teng, W. Li, J. Zhang, X. Cheng, X. Li, X. Han, Z. Xia, H. Deng, et al. Targeted Disruption of Smad4 in Mouse Epidermis Results in Failure of Hair Follicle Cycling and Formation of Skin Tumors Cancer Res., October 1, 2005; 65(19): 8671 - 8678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Han, Y.-i. Tsukada, E. Hara, N. Kitamura, and T. Tanaka Hepatocyte Growth Factor Induces Redistribution of p21CIP1 and p27KIP1 through ERK-dependent p16INK4a Up-regulation, Leading to Cell Cycle Arrest at G1 in HepG2 Hepatoma Cells J. Biol. Chem., September 9, 2005; 280(36): 31548 - 31556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Close, B. Gumuscu, and T. A. Reh Retinal neurons regulate proliferation of postnatal progenitors and Muller glia in the rat retina via TGF{beta} signaling Development, July 1, 2005; 132(13): 3015 - 3026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kotoshiba, T. Kamura, T. Hara, N. Ishida, and K. I. Nakayama Molecular Dissection of the Interaction between p27 and Kip1 Ubiquitylation-promoting Complex, the Ubiquitin Ligase That Regulates Proteolysis of p27 in G1 Phase J. Biol. Chem., May 6, 2005; 280(18): 17694 - 17700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Gadal, A Starzec, C Bozic, C Pillot-Brochet, S Malinge, V Ozanne, J Vicenzi, L Buffat, G Perret, F Iris, et al. Integrative analysis of gene expression patterns predicts specific modulations of defined cell functions by estrogen and tamoxifen in MCF7 breast cancer cells J. Mol. Endocrinol., February 1, 2005; 34(1): 61 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kotake, K. Nakayama, N. Ishida, and K. I. Nakayama Role of Serine 10 Phosphorylation in p27 Stabilization Revealed by Analysis of p27 Knock-in Mice Harboring a Serine 10 Mutation J. Biol. Chem., January 14, 2005; 280(2): 1095 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Zhang, L. D. Nielsen, J. J. Lucas, and R. J. Mason Transforming Growth Factor-{beta} Antagonizes Alveolar Type II Cell Proliferation Induced by Keratinocyte Growth Factor Am. J. Respir. Cell Mol. Biol., December 1, 2004; 31(6): 679 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Box and D. J. Demetrick Cell cycle kinase inhibitor expression and hypoxia-induced cell cycle arrest in human cancer cell lines Carcinogenesis, December 1, 2004; 25(12): 2325 - 2335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Sheikh, C. J.A. Hirst, Y. Jin, M. E. Bock, R. R. Fandrich, B. E. Nickel, B. W. Doble, E. Kardami, and P. A. Cattini Inhibition of TGF{beta} signaling potentiates the FGF-2-induced stimulation of cardiomyocyte DNA synthesis Cardiovasc Res, December 1, 2004; 64(3): 516 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Sherr and J. M. Roberts Living with or without cyclins and cyclin-dependent kinases Genes & Dev., November 15, 2004; 18(22): 2699 - 2711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.S. Prime, M. Pring, M. Davies, and I.C. Paterson TGF-{beta} SIGNAL TRANSDUCTION IN ORO-FACIAL HEALTH AND NON-MALIGNANT DISEASE (PART I) Crit. Rev. Oral. Biol. Med., November 1, 2004; 15(6): 324 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Scandura, P. Boccuni, J. Massague, and S. D. Nimer Transforming growth factor {beta}-induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation PNAS, October 19, 2004; 101(42): 15231 - 15236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Song, J. Cooperman, D. L. Letting, G. A. Blobel, and J. K. Choi Identification of Cyclin D3 as a Direct Target of E2A Using DamID Mol. Cell. Biol., October 1, 2004; 24(19): 8790 - 8802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ougolkov, B. Zhang, K. Yamashita, V. Bilim, M. Mai, S. Y. Fuchs, and T. Minamoto Associations Among {beta}-TrCP, an E3 Ubiquitin Ligase Receptor, {beta}-Catenin, and NF-{kappa}B in Colorectal Cancer J Natl Cancer Inst, August 4, 2004; 96(15): 1161 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saika, Y. Muragaki, Y. Okada, T. Miyamoto, Y. Ohnishi, A. Ooshima, and W. W.-Y. Kao Sonic Hedgehog Expression and Role in Healing Corneal Epithelium Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2577 - 2585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Gao, D. C. Flynn, Z. Zhang, X.-S. Zhong, V. Walker, K. J. Liu, X. Shi, and B.-H. Jiang G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells Am J Physiol Cell Physiol, August 1, 2004; 287(2): C281 - C291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yoshida, S. Kase, K. Nakayama, H. Nagahama, T. Harada, H. Ikeda, C. Harada, J. Imaki, K. Ohgami, K. Shiratori, et al. Involvement of p27KIP1 in the Proliferation of the Developing Corneal Endothelium Invest. Ophthalmol. Vis. Sci., July 1, 2004; 45(7): 2163 - 2167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kikuchi, D. L. Harris, Y. Obara, T. Senoo, and N. C. Joyce p27kip1 Antisense-Induced Proliferative Activity of Rat Corneal Endothelial Cells Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 1763 - 1770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Benzeno, G. Narla, J. Allina, G. Z. Cheng, H. L. Reeves, M. S. Banck, J. A. Odin, J. A. Diehl, D. Germain, and S. L. Friedman Cyclin-Dependent Kinase Inhibition by the KLF6 Tumor Suppressor Protein through Interaction with Cyclin D1 Cancer Res., June 1, 2004; 64(11): 3885 - 3891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Di Carlo, R. De Mori, F. Martelli, G. Pompilio, M. C. Capogrossi, and A. Germani Hypoxia Inhibits Myogenic Differentiation through Accelerated MyoD Degradation J. Biol. Chem., April 16, 2004; 279(16): 16332 - 16338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Denicourt and S. F. Dowdy Cip/Kip proteins: more than just CDKs inhibitors Genes & Dev., April 15, 2004; 18(8): 851 - 855. [Full Text] [PDF]
|
|
|
|
|
|
J. P. Frederick, N. T. Liberati, D. S. Waddell, Y. Shi, and X.-F. Wang Transforming Growth Factor {beta}-Mediated Transcriptional Repression of c-myc Is Dependent on Direct Binding of Smad3 to a Novel Repressive Smad Binding Element Mol. Cell. Biol., March 15, 2004; 24(6): 2546 - 2559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-Y. Cao, Y. Lee, N.-P. Feng, R. A. Al-Qawasmeh, S. Viau, X.-P. Gu, L. Lau, H. Jin, M. Wang, A. Vassilakos, et al. NC381, a Novel Anticancer Agent, Arrests the Cell Cycle in G0-G1 and Inhibits Lung Tumor Cell Growth in Vitro and in Vivo J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 538 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Hu, G.-F. Hu, Y. Kim, T. Tsuji, J. McBride, P. Hinds, and D. T. W. Wong Role of p12CDK2-AP1 in Transforming Growth Factor-{beta}1-Mediated Growth Suppression Cancer Res., January 15, 2004; 64(2): 490 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Hendricks, F. Shanahan, and E. Lees Role for BRG1 in Cell Cycle Control and Tumor Suppression Mol. Cell. Biol., January 1, 2004; 24(1): 362 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Denicourt and S. F. Dowdy Another twist in the transforming growth factor {beta}-induced cell-cycle arrest chronicle PNAS, December 23, 2003; 100(26): 15290 - 15291. [Full Text] [PDF]
|
|
|
|
|
|
N. A. Bhowmick, M. Ghiassi, M. Aakre, K. Brown, V. Singh, and H. L. Moses From the Cover: TGF-{beta}-induced RhoA and p160ROCK activation is involved in the inhibition of Cdc25A with resultant cell-cycle arrest PNAS, December 23, 2003; 100(26): 15548 - 15553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A A Khan, P D Abel, K S Chaudhary, Z Gulzar, G W H Stamp, and E-N Lalani Inverse correlation between high level expression of cyclin E and proliferation index in transitional cell carcinoma of the bladder Mol. Pathol., December 1, 2003; 56(6): 353 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Deng, F. Gao, and W. S. May Jr. Bcl2 retards G1/S cell cycle transition by regulating intracellular ROS Blood, November 1, 2003; 102(9): 3179 - 3185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Yang, Y.-Y. Wen, C.-H. Chen, G. Lozano, and M.-H. Lee 14-3-3{sigma} Positively Regulates p53 and Suppresses Tumor Growth Mol. Cell. Biol., October 15, 2003; 23(20): 7096 - 7107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhou, I. Park, M. Pins, J. M. Kozlowski, B. Jovanovic, J. Zhang, C. Lee, and K. Ilio Dual Regulation of Proliferation and Growth Arrest in Prostatic Stromal Cells by Transforming Growth Factor-{beta}1 Endocrinology, October 1, 2003; 144(10): 4280 - 4284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Siegel, W. Shu, and J. Massague Mad Upregulation and Id2 Repression Accompany Transforming Growth Factor (TGF)-{beta}-mediated Epithelial Cell Growth Suppression J. Biol. Chem., September 12, 2003; 278(37): 35444 - 35450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Long, I. Matsuura, D. He, G. Wang, K. Shuai, and F. Liu Repression of Smad transcriptional activity by PIASy, an inhibitor of activated STAT PNAS, August 19, 2003; 100(17): 9791 - 9796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Kothapalli, S. A. Stewart, E. M. Smyth, I. Azonobi, D. J. Rader, E. Pure, and R. K. Assoian Prostacylin Receptor Activation Inhibits Proliferation of Aortic Smooth Muscle Cells by Regulating cAMP Response Element-Binding Protein- and Pocket Protein-Dependent Cyclin A Gene Expression Mol. Pharmacol., August 1, 2003; 64(2): 249 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tadlock, Y. Yamagiwa, J. Hawker, C. Marienfeld, and T. Patel Transforming growth factor-{beta} inhibition of proteasomal activity: a potential mechanism of growth arrest Am J Physiol Cell Physiol, August 1, 2003; 285(2): C277 - C285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Paternot, K. Coulonval, J. E. Dumont, and P. P. Roger Cyclic AMP-dependent Phosphorylation of Cyclin D3-bound CDK4 Determines the Passage through the Cell Cycle Restriction Point in Thyroid Epithelial Cells J. Biol. Chem., July 11, 2003; 278(29): 26533 - 26540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Gelen, G. O. Elpek, N. H. Aksoy, M. Ogus, and N. Keles p27 Labeling Index and Proliferation in Gastrointestinal Stromal Tumors: Correlations with Clinicopathologic Factors and Recurrence Jpn. J. Clin. Oncol., July 1, 2003; 33(7): 346 - 352. [Abstract] [Full Text] [PDF]
|
|
