CDK inhibitors: positive and negative regulators of G1-phase progression

Sherr, C. J.; Roberts, J. M.

doi:10.1101/gad.13.12.1501

Cited by 6,115Cancer-related Molecular PathwaysMicrotubule and mitosis dynamicsProtein Kinase Regulation and GTPase Signaling

CDK inhibitors: positive and negative regulators of G1-phase progression

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Sherr, C. J., Roberts, J. M.·1999·Genes & Development

DOI 10.1101/gad.13.12.1501

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Abstract

Mitogen-dependent progression through the first gap phase (G1) and initiation of DNA synthesis (S phase) during the mammalian cell division cycle are cooperatively regulated by several classes of cyclin-dependent kinases (CDKs) whose activities are in turn constrained by CDK inhibitors (CKIs). CKIs that govern these events have been assigned to one of two families based on their structures and CDK targets. The first class includes the INK4 proteins (inhibitors of CDK4), so named for their ability to specifically inhibit the catalytic subunits of CDK4 and CDK6. Four such proteins [p16 (Serrano et al. 1993), p15 (Hannon and Beach 1994), p18 (Guan et al. 1994; Hirai et al. 1995), and p19 (Chan et al. 1995; Hirai et al. 1995)] are composed of multiple ankyrin repeats and bind only to CDK4 and CDK6 but not to other CDKs or to D-type cyclins. The INK4 proteins can be contrasted with more broadly acting inhibitors of the Cip/Kip family whose actions affect the activities of cyclin D-, E-, and A-dependent kinases. The latter class includes p21 (Gu et al. 1993; Harper et al. 1993; El-Deiry et al. 1993; Xiong et al. 1993a; Dulic et al. 1994; Noda et al. 1994), p27 (Polyak et al. 1994a,b; Toyoshima and Hunter 1994), and p57 (Lee et al. 1995; Matsuoka et al. 1995), all of which contain characteristic motifs within their amino-terminal moieties that enable them to bind both to cyclin and CDK subunits (Chen et al. 1995, 1996; Nakanishi et al. 1995; Warbrick et al. 1995; Lin et al. 1996; Russo et al. 1996). Based largely on in vitro experiments and in vivo overexpression studies, CKIs of the Cip/Kip family were initially thought to interfere with the activities of cyclin D-, E-, and A-dependent kinases. More recent work has altered this view and revealed that although the Cip/Kip proteins are potent inhibitors of cyclin Eand A-dependent CDK2, they act as positive regulators of cyclin Ddependent kinases. This challenges previous assumptions about how the G1/S transition of the mammalian cell cycle is governed, helps explain some enigmatic features of cell cycle control that also involve the functions of the retinoblastoma protein (Rb) and the INK4 proteins, and changes our thinking about how either p16 loss or overexpression of cyclin D-dependent kinases contribute to cancer. Here we focus on the biochemical interactions that occur between CKIs and cyclin Dand E-dependent kinases in cultured mammalian cells, emphasizing the manner by which different positive and negative regulators of the cell division cycle cooperate to govern the G1-to-S transition. To gain a more comprehensive understanding of the biology of CDK inhibitors, readers are encouraged to refer to a rapidly emerging but already extensive literature (for review, see Elledge and Harper 1994; Sherr and Roberts 1995; Chellappan et al. 1998; Hengst and Reed 1998a; Kiyokawa and Koff 1998; Nakayama 1998; Ruas and Peters 1998).

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“In contrast, we found that incubation of AHPs with IL-1β induces a dramatic decline in levels of cyclin D1, a cell cycle regulatory protein that controls specific cyclin-dependent kinases such as cdk4 (31).”
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From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Sherr and Roberts, 1999
p21Cip1 and p27Kip1 facilitate cyclin D-CDK assembly and nuclear import without inhibiting CDK4/6 kinase activity.
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From Targeting CDK4 and CDK6: From Discovery to Therapy (2016) · cites this paper as [41]
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From Targeting CDK4 and CDK6: From Discovery to Therapy (2016) · cites this paper as [41]

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Background
Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation
Knoblich, J. A., Sauer, K., Jones, L., Richardson, H. E., Saint, R. B., & Lehner, C. F. (1994) · Cell · doi:10.1016/0092-8674(94)90239-9 · Cited by 542 · see citing works
Deregulated Expression of E2F-1 Induces S-Phase Entry and Leads to Apoptosis
Shan, B., & Lee, W. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8166 · Cited by 529 · see citing works
Tumour-derived p16 alleles encoding proteins defective in cell-cycle inhibition
Koh, J., Enders, G. H., David Dynlacht, B., & Harlow, E. (1995) · Nature · doi:10.1038/375506a0 · Cited by 516 · see citing works
Toward an understanding of the functional complexity of the E2F and retinoblastoma families.
Nevins, J. R. (1998) · PubMed · Cited by 514 · see citing works
Cell cycle control of DNA replication
Stillman, B. (1996) · Science · doi:10.1126/science.274.5293.1659 · Cited by 507 · see citing works
Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation.Preprint
Xiong, Y., Zhang, H., & Beach, D. (1993) · Genes & Development · doi:10.1101/gad.7.8.1572 · Cited by 507 · see citing works
Assembly of cyclin D-dependent kinase and titration of p27 Kip1 regulated by mitogen-activated protein kinase kinase (MEK1)
Cheng, M., Sexl, V., Sherr, C. J., & Roussel, M. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.3.1091 · Cited by 496 · see citing works
Self-citation
Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation.Preprint
Clurman, B. E., Sheaff, R. J., Thress, K. S., Groudine, M. T., & Roberts, J. M. (1996) · Genes & Development · doi:10.1101/gad.10.16.1979 · Cited by 488 · see citing works
Self-citation
Evidence that the G1-S and G2-M transitions are controlled by different cdc2 proteins in higher eukaryotes
Fang, F., & Newport, J. W. (1991) · Cell · doi:10.1016/0092-8674(91)90117-h · Cited by 483 · see citing works
Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4
Stepanova, L., Leng, X., Parker, S. B., & Harper, J. W. (1996) · Genes & Development · doi:10.1101/gad.10.12.1491 · Cited by 483 · see citing works
Growth suppression by p16ink4 requires functional retinoblastoma protein
Medema, R. H., Herrera, R. E., Lam, F., & Weinberg, R. A. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.14.6289 · Cited by 433 · see citing works
pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes
Hurford, R. K., Cobrinik, D., Lee, M. H., & Dyson, N. (1997) · Genes & Development · doi:10.1101/gad.11.11.1447 · Cited by 431 · see citing works
Ras Links Growth Factor Signaling to the Cell Cycle Machinery via Regulation of Cyclin D1 and the Cdk Inhibitor p27KIP1
Aktaş, H., Cai, H., & Cooper, G. M. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.7.3850 · Cited by 410 · see citing works
Sustained activation of extracellular-signal-regulated kinase 1 (ERK1) is required for the continued expression of cyclin D1 in G1 phase
Weber, J. D., Raben, D. M., Phillips, P. J., & Baldassare, J. J. (1997) · Biochemical Journal · doi:10.1042/bj3260061 · Cited by 407 · see citing works
The retinoblastoma susceptibility gene product undergoes cell cycle-dependent dephosphorylation and binding to and release from SV40 large T
Ludlow, J. W., Shon, J. C., Pipas, J. M., Livingston, D. M., & DeCaprio, J. A. (1990) · Cell · doi:10.1016/0092-8674(90)90590-b · Cited by 381 · see citing works
Cyclin E-induced S phase without activation of the pRb/E2F pathway.Preprint
Lukáš, J., Herzinger, T., Hansen, K. H., Moroni, M. C., Resnitzky, D., Helin, K., Reed, S. I., & Bártek, J. (1997) · Genes & Development · doi:10.1101/gad.11.11.1479 · Cited by 375 · see citing works
Cyclin D1 Is Dispensable for G 1 Control in Retinoblastoma Gene-Deficient Cells Independently of cdk4 Activity
Lukas, J., Bártková, J., Rohde, M., Strauss, M., & Bartek, J. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.5.2600 · Cited by 366 · see citing works
Activation of cyclin E/CDK2 is coupled to site‐specific autophosphorylation and ubiquitin‐dependent degradation of cyclin E.
Won, K. A., & Reed, S. I. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00793.x · Cited by 360 · see citing works
Ras signalling linked to the cell-cycle machinery by the retinoblastoma protein
Peeper, D. S., Upton, T. M., Ladha, M. H., Neuman, E., Zalvide, J. B., Bernards, R., DeCaprio, J. A., & Ewen, M. E. (1997) · Nature · doi:10.1038/386177a0 · Cited by 357 · see citing works
Active Transcriptional Repression by the Rb–E2F Complex Mediates G1 Arrest Triggered by p16INK4a, TGFβ, and Contact Inhibition
Zhang, H. S., Postigo, A. A., & Dean, D. C. (1999) · Cell · doi:10.1016/s0092-8674(00)80714-x · Cited by 349 · see citing works
Cyclin encoded by KS herpesvirus
Chang, Y., Moore, P. S., Talbot, S. J., et al. (1996) · Nature · doi:10.1038/382410a0 · Cited by 345 · see citing works
Identification of Human and Mouse p19, a Novel CDK4 and CDK6 Inhibitor with Homology to p16ink4
Chan, F. K. M., Zhang, J., Cheng, L. E., Shapiro, D. N., & Winoto, A. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.5.2682 · Cited by 339 · see citing works
Herpes viral cyclin/Cdk6 complexes evade inhibition by CDK inhibitor proteins
Swanton, C., Mann, D. J., Fleckenstein, B., Neipel, F., Peters, G. G., & Jones, N. (1997) · Nature · doi:10.1038/36606 · Cited by 334 · see citing works
The subcellular locations of p15(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with cdk4 and cdk2.Preprint
Reynisdóttir, I., & Massagué, J. (1997) · Genes & Development · doi:10.1101/gad.11.4.492 · Cited by 332 · see citing works
D-Type Cyclin-Dependent Kinase Activity in Mammalian Cells
Matsushime, H., Quelle, D. E., Shurtleff, S. A., et al. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.2066-2076.1994 · Cited by 324 · see citing works
Cdk inhibitors: on the threshold of checkpoints and development
Elledge, S. J., & Harper, J. W. (1994) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(94)90055-8 · Cited by 321 · see citing works
The Prognostic Significance of Altered Cyclin-Dependent Kinase Inhibitors in Human Cancer
Tsihlias, J., Kapusta, L. R., & Slingerland, J. M. (1999) · Annual Review of Medicine · doi:10.1146/annurev.med.50.1.401 · Cited by 320 · see citing works
Cyclin-Binding Motifs Are Essential for the Function of p21 CIP1 
Chen, J., Saha, P., Kornbluth, S., Dynlacht, B. D., & Dutta, A. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4673 · Cited by 320 · see citing works
Cyclin/Cdk-Dependent Initiation of DNA Replication in a Human Cell-Free System
Krude, T., Jackman, M. R., Pines, J., & Laskey, R. A. (1997) · Cell · doi:10.1016/s0092-8674(00)81863-2 · Cited by 310 · see citing works
Altered Cell Cycle Kinetics, Gene Expression, and G 1 Restriction Point Regulation in Rb -Deficient Fibroblasts
Herrera, R. E., Sah, V. P., Williams, B. O., Mäkelä, T. P., Weinberg, R. A., & Jacks, T. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.5.2402 · Cited by 302 · see citing works
Induction of cyclin D1 overexpression by activated ras.
Filmus, J., Robles, A. I., Shi, W., Wong, M. J. H., Colombo, L. L., & Conti, C. J. (1994) · PubMed · Cited by 295 · see citing works
Hypo-phosphorylation of the retinoblastoma protein (pRb) by cyclin D:Cdk4/6 complexes results in active pRb
Ezhevsky, S. A., Nagahara, H., Vocero-Akbani, A. M., Gius, D. R., Wei, M. C., & Dowdy, S. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10699 · Cited by 280 · see citing works
Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 with cyclin A-Cdk2 and cyclin D2-Cdk4
Blain, S. W., Montalvo, E., & Massagué, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.41.25863 · Cited by 279 · see citing works
Cell Cycle Control of DNA Replication by a Homologue from Human Cells of the p34 cdc2 Protein Kinase
D’Urso, G., Marraccino, R. L., Marshak, D. R., & Roberts, J. M. (1990) · Science · doi:10.1126/science.2173140 · Cited by 279 · see citing works
Self-citation
A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen
Warbrick, E., Lane, D. P., Glover, D. M., & Cox, L. S. (1995) · Current Biology · doi:10.1016/s0960-9822(95)00058-3 · Cited by 278 · see citing works
SCF and APC: the Yin and Yang of cell cycle regulated proteolysis
Peters, J. (1998) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(98)80119-1 · Cited by 271 · see citing works
Cyclin A is required in S phase in normal epithelial cells
Zindy, F., Lamas, E., Chenivesse, X., Sobczak‐Thépot, J., Wang, J., Fesquet, D., Henglein, B., & Bréchot, C. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)91851-g · Cited by 271 · see citing works
DNA tumor virus oncoproteins and retinoblastoma gene mutations share the ability to relieve the cell's requirement for cyclin D1 function in G1.
Lukáš, J., Müller, H., Bártková, J., Spitkovsky, D., Kjerulff, A. A., Jansen‐Dürr, P., Strauss, M., & Bártek, J. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.125.3.625 · Cited by 269 · see citing works
Specific Enzymatic Dephosphorylation of the Retinoblastoma Protein
Ludlow, J. W., Glendening, C. L., Livingston, D. M., & DeCarprio, J. A. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.1.367 · Cited by 258 · see citing works
RB kinases and RB-binding proteins: new points of view
Taya, Y. (1997) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)10070-0 · Cited by 257 · see citing works
Collaboration of G1 cyclins in the functional inactivation of the retinoblastoma protein.Preprint
Hatakeyama, M., Brill, J. A., Fink, G. R., & Weinberg, R. A. (1994) · Genes & Development · doi:10.1101/gad.8.15.1759 · Cited by 250 · see citing works
Induced Expression of p16INK4a Inhibits Both CDK4- and CDK2-Associated Kinase Activity by Reassortment of Cyclin-CDK-Inhibitor Complexes
McConnell, B. B., Gregory, F. J., Stott, F. J., Hara, E., & Peters, G. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.1981 · Cited by 238 · see citing works
Formation of p27-CDK complexes during the human mitotic cell cycle.
Soos, T. J., Kiyokawa, H., Yan, J. S., Rubin, M. S., Giordano, A., DeBlasio, A., Bottega, S., Wong, B., Mendelsohn, J. M., & Koff, A. (1996) · PubMed · Cited by 238 · see citing works
Expression of NPAT, a novel substrate of cyclin E-CDK2, promotes S-phase entryPreprint
Zhao, J., Dynlacht, B. D., Imai, T., Hori, T.-A., & Harlow, E. E. (1998) · Genes & Development · doi:10.1101/gad.12.4.456 · Cited by 223 · see citing works
Cyclin E and c‐Myc promote cell proliferation in the presence of p16INK4a and of hypophosphorylated retinoblastoma family proteins
Alevizopoulos, K., Vlach, J., Hennecke, S., & Amati, B. B. (1997) · The EMBO Journal · doi:10.1093/emboj/16.17.5322 · Cited by 202 · see citing works
Early events in DNA replication require cyclin E and are blocked by p21CIP1.
Jackson, P. K., Chevalier, S., Philippe, M., & Kirschner, M. W. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.130.4.755 · Cited by 200 · see citing works
A cdc2-like protein is involved in the initiation of DNA replication in Xenopus egg extracts
Blow, J. J., & Nurse, P. (1990) · Cell · doi:10.1016/0092-8674(90)90261-c · Cited by 200 · see citing works
Regulation of the cell cycle machinery by oncogenic ras.
Winston, J. T., Coats, S., Wang, Y.-Z., & Pledger, W. J. (1996) · PubMed · Cited by 198 · see citing works
Cyclin A is required for the onset of DNA replication in mammalian fibroblasts
Girard, F., Strausfeld, U. P., Fernandez, A., & Lamb, N. J. C. (1992) · Trends in Cell Biology · doi:10.1016/0962-8924(92)90073-v · Cited by 189 · see citing works
Identification of the active region of the DNA synthesis inhibitory gene p21Sdi1/CIP1/WAF1.
Nakanishi, M., Robetorye, R. S., Adami, G. R., Pereira‐Smith, O. M., & Smith, J. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07031.x · Cited by 179 · see citing works
Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to cyclins.
Hall, M., Bates, S., & Peters, G. J. (1995) · PubMed · Cited by 178 · see citing works
Degradation of p27Kip cdk inhibitor triggered by Kaposi's sarcoma virus cyclin–cdk6 complex
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Induction of cell cycle arrest and B cell terminal differentiation by CDK inhibitor p18(INK4c) and IL-6.
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Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors
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Deregulated Expression of E2F-1 Induces S-Phase Entry and Leads to Apoptosis
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Induction of Cell Proliferation in Quiescent NIH 3T3 Cells by Oncogenic c-Raf-1
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Inhibitors of the Cip/Kip Family
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Distinct sub‐populations of the retinoblastoma protein show a distinct pattern of phosphorylation.
Mittnacht, S., Lees, J. A., Desai, D. M., Harlow, E., Morgan, D. O., & Weinberg, R. A. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06241.x · Cited by 150 · see citing works
Modulation of p27Kip1 levels by the cyclin encoded by Kaposi's sarcoma‐associated herpesvirus
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Retinoblastoma protein meets chromatin
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Both cyclin A and cyclin E have S-phase promoting (SPF) activity in Xenopus egg extracts
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Physical Interaction of Mammalian CDC37 with CDK4
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Induction of p21 WAF1/CIP1 and Inhibition of Cdk2 Mediated by the Tumor Suppressor p16 INK4a
Mitra, J., Dai, C. Y., Somasundaram, K., El‐Deiry, W. S., Satyamoorthy, K., Herlyn, M., & Enders, G. H. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3916 · Cited by 124 · see citing works
Accumulation of p16INK4a in mouse fibroblasts as a function of replicative senescence and not of retinoblastoma gene status
Palmero, I., McConnell, B. B., Parry, D., Brookes, S., Hara, E., Bates, S., Jat, P., & Peters, G. G. (1997) · Oncogene · doi:10.1038/sj.onc.1201212 · Cited by 123 · see citing works
Expression of INK4 inhibitors of cyclin D-dependent kinases during mouse brain development.
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Requirement of Cyclin E-Cdk2 Inhibition in p16 INK4a -Mediated Growth Suppression
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Analysis of Wild-Type and Mutant p21 WAF-1 Gene Activities
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Role of Cyclin-Dependent Kinases and Their Inhibitors in Cellular Differentiation and Development
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Active cdk6 complexes are predominantly nuclear and represent only a minority of the cdk6 in T cells
Mahony, D., Parry, D. A. D., & Lees, E. M. (1998) · Oncogene · doi:10.1038/sj.onc.1201570 · Cited by 99 · see citing works
Specific Enzymatic Dephosphorylation of the Retinoblastoma Protein
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Interaction between Cdc37 and Cdk4 in human cells
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Identification of a substrate-targeting domain in cyclin E necessary for phosphorylation of the retinoblastoma protein
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Self-citation
Coupled Transcriptional and Translational Control of Cyclin-Dependent Kinase Inhibitor p18 INK4c Expression during Myogenesis
Phelps, D. E., Hsiao, K., Li, Y., Hu, N., Franklin, D. S., Westphal, E., Lee, E. Y.-H. P., & Xiong, Y. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.4.2334 · Cited by 86 · see citing works
Aberrations of the G1- and G1/S-regulating genes in human cancer
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Mutual requirement of CDK4 and Myc in malignant transformation: evidence for cyclin D1/CDK4 and p16INK4A as upstream regulators of Myc
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Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle
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Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts
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Functional domains in cyclin D1: pRb-kinase activity is not essential for transformation
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Inhibition of p53-Mediated Growth Arrest by Overexpression of Cyclin-Dependent Kinases
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p21WAF1/CIP1 mutants deficient in inhibiting cyclin-dependent kinases (CDKs) can promote assembly of active cyclin D/CDK4(6) complexes in human tumor cells.
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Roles of Cyclin-Dependent Kinase Inhibitors: Lessons from Knockout Mice
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Inflammation, antichymotrypsin, and lipid metabolism: autogenic etiology of alzheimer's disease
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Induction of Cell Cycle Arrest and B Cell Terminal Differentiation by CDK Inhibitor p18 INK4c and IL-6
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Medema, R.H., R.E. Herrera, F. Lam, and R.A. Weinberg. 1995. Growth suppression by p16 ink4 requires functional retino- blastoma protein. Proc. Natl. Acad. Sci. 92: 6289-6293.

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Cellular senescence: when bad things happen to good cells
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Goel, S., DeCristo, M. J., Watt, A. C., BrinJones, H., Sceneay, J., Li, B. B., Khan, N., Ubellacker, J. M., Xie, S., Metzger-Filho, O., et al. (2017) · Nature · doi:10.1038/nature23465 · Cited by 1,513 · see citing works
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Cyclin D as a therapeutic target in cancer
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Homeostasis of Naive and Memory T Cells
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Authors: Sherr, C. J., & Roberts, J. M.
Affiliations: St. Jude Children's Research Hospital (US)
ORCID: Sherr, C. J.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 1999-06-15
Volume: 13
Issue: 12
Pages: 1501-1512
ISSN: 0890-9369 (ISSN-L)
DOI: 10.1101/gad.13.12.1501
OpenAlex: W2121619780
Cited by: 6,115
References: 151
Citations by year: 2026: 71 · 2025: 97 · 2024: 94 · 2023: 122 · 2022: 137 · 2021: 148 · 2020: 149 · 2019: 142 · 2018: 146 · 2017: 160 · 2016: 154 · 2015: 208 · 2014: 207 · 2013: 234 · 2012: 255
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: cyclin-dependent kinase inhibitors, cyclin-dependent kinases, G1 phase progression, cell cycle regulation, p16, p21, p27, p57, CDK4, CDK6, cyclin D, cyclin E, cyclin A, ankyrin repeats, cell cycle checkpoint control, tumor suppressor
MeSH terms: Animals, Carrier Proteins, Catalysis, Cell Cycle, Enzyme Inhibitors, Humans, Microtubule-Associated Proteins, Neoplasms, G1 Phase, Cyclins, Cell Cycle Proteins, Cyclin-Dependent Kinases, Cyclin E, Cyclin-Dependent Kinase Inhibitor p16, Holoenzymes, Tumor Suppressor Proteins, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinase Inhibitor p19, Cyclin D

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CDK inhibitors: positive and negative regulators of G1-phase progression

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