cyclin dependent kinase inhibitor proteins


Summary: A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.

Top Publications

  1. Mizutani M, Naganuma T, Tsutsumi K, Saitoh Y. The syncytium-specific expression of the Orysa;KRP3 CDK inhibitor: implication of its involvement in the cell cycle control in the rice (Oryza sativa L.) syncytial endosperm. J Exp Bot. 2010;61:791-8 pubmed publisher
    ..These data suggest that Orysa;KRP3 is involved in cell cycle control of syncytial endosperm...
  2. Raje N, Hideshima T, Mukherjee S, Raab M, Vallet S, Chhetri S, et al. Preclinical activity of P276-00, a novel small-molecule cyclin-dependent kinase inhibitor in the therapy of multiple myeloma. Leukemia. 2009;23:961-70 pubmed publisher
    ..Finally, in vivo efficacy of P276-00 was confirmed in an MM xenograft model. These studies form the basis of an ongoing phase I study in the treatment of relapsed/refractory MM. ..
  3. Croucher D, Rickwood D, Tactacan C, Musgrove E, Daly R. Cortactin modulates RhoA activation and expression of Cip/Kip cyclin-dependent kinase inhibitors to promote cell cycle progression in 11q13-amplified head and neck squamous cell carcinoma cells. Mol Cell Biol. 2010;30:5057-70 pubmed publisher
  4. Hyvelin J, Maurel B, Uzbekov R, Motterlini R, Lermusiaux P. Hemin prevents in-stent stenosis in rat and rabbit models by inducing heme-oxygenase-1. J Vasc Surg. 2010;51:417-28 pubmed publisher
    ..We assessed the ability of hemin, a potent HO-1 inducer, to reduce in-stent stenosis without compromising re-endothelialization...
  5. Mertlíková Kaiserová H, Votruba I, Matousová M, Holy A, Hájek M. Role of caspases and CD95/Fas in the apoptotic effects of a nucleotide analog PMEG in CCRF-CEM cells. Anticancer Res. 2010;30:2791-8 pubmed
    ..PMEG-induced apoptosis is caspase- and CD95/Fas-independent. ..
  6. Cardone A, Hassan S, Albers R, Sriram R, Pant H. Structural and dynamic determinants of ligand binding and regulation of cyclin-dependent kinase 5 by pathological activator p25 and inhibitory peptide CIP. J Mol Biol. 2010;401:478-92 pubmed publisher
    ..These changes provide a rationale for the observed high affinity and enhanced inhibitory action of CIP when compared to either p25 or the physiological activators of cdk5. ..
  7. Anzola J, Sieberer T, Ortbauer M, Butt H, Korbei B, Weinhofer I, et al. Putative Arabidopsis transcriptional adaptor protein (PROPORZ1) is required to modulate histone acetylation in response to auxin. Proc Natl Acad Sci U S A. 2010;107:10308-13 pubmed publisher
    ..Collectively, our findings support a model in which translation of positional signals into developmental cues involves adjustments in chromatin modifications that orchestrate auxin effects on cell proliferation. ..
  8. Hürlimann H, Pinson B, Stadler Waibel M, Zeeman S, Freimoser F. The SPX domain of the yeast low-affinity phosphate transporter Pho90 regulates transport activity. EMBO Rep. 2009;10:1003-8 pubmed publisher
    ..This work suggests that the SPX domain inhibits low-affinity phosphate transport through a physical interaction with Spl2. ..
  9. Trávníček Z, Popa I, Cajan M, Zboril R, Krystof V, Mikulík J. The first iron(III) complexes with cyclin-dependent kinase inhibitors: Magnetic, spectroscopic (IR, ES+ MS, NMR, (57)Fe Mössbauer), theoretical, and biological activity studies. J Inorg Biochem. 2010;104:405-17 pubmed publisher
    ..In addition, the X-ray structure of 2-chloro-6-benzylamino-9-isopropylpurine, i.e. a precursor for the preparation of L(1), L(4) and L(5), is also described. ..

More Information


  1. Hao B, Oehlmann S, Sowa M, Harper J, Pavletich N. Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell. 2007;26:131-43 pubmed
  2. Laine H, Sulg M, Kirjavainen A, Pirvola U. Cell cycle regulation in the inner ear sensory epithelia: role of cyclin D1 and cyclin-dependent kinase inhibitors. Dev Biol. 2010;337:134-46 pubmed publisher
    ..Thus, cyclin D1 critically contributes to the proliferative plasticity of supporting cells. These data suggest that targeted cyclin D1 induction in supporting cells might be an avenue for proliferative regeneration in the inner ear. ..
  3. Lee B, Lee E, Kim D, Park S, Kim W, Moon S. Inhibition of proliferation and migration by piceatannol in vascular smooth muscle cells. Toxicol In Vitro. 2009;23:1284-91 pubmed publisher
    ..Overall, these results demonstrate that piceatannol inhibits proliferation and migration of VSMC treated with TNF-alpha. Therefore, piceatannol may be an effective therapeutic approach to treat atherosclerosis. ..
  4. Chen S, Law C, Gardner D. Vitamin D-dependent suppression of endothelin-induced vascular smooth muscle cell proliferation through inhibition of CDK2 activity. J Steroid Biochem Mol Biol. 2010;118:135-41 pubmed publisher
  5. Mittag T, Kay L, Forman Kay J. Protein dynamics and conformational disorder in molecular recognition. J Mol Recognit. 2010;23:105-16 pubmed publisher
    ..The nature of these interactions is not well understood yet but advancements in the structural characterization of disordered states will help us gain insights into their function and their implications for health and disease. ..
  6. Kool J, Uren A, Martins C, Sie D, de Ridder J, Turner G, et al. Insertional mutagenesis in mice deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 reveals cancer gene interactions and correlations with tumor phenotypes. Cancer Res. 2010;70:520-31 pubmed publisher
  7. Sadowski M, Suryadinata R, Lai X, Heierhorst J, Sarcevic B. Molecular basis for lysine specificity in the yeast ubiquitin-conjugating enzyme Cdc34. Mol Cell Biol. 2010;30:2316-29 pubmed publisher
  8. George J, Banik N, Ray S. Knockdown of hTERT and concurrent treatment with interferon-gamma inhibited proliferation and invasion of human glioblastoma cell lines. Int J Biochem Cell Biol. 2010;42:1164-73 pubmed publisher
    ..Therefore, the combination of hTERT siRNA and IFN-gamma offers a potential therapeutic strategy for controlling growth of human glioblastoma cells. ..
  9. Solc P, Schultz R, Motlik J. Prophase I arrest and progression to metaphase I in mouse oocytes: comparison of resumption of meiosis and recovery from G2-arrest in somatic cells. Mol Hum Reprod. 2010;16:654-64 pubmed publisher
    ..These common features include CDC14B-dependent activation of APC-CDH1 in prophase I arrested oocytes or G2-arrested somatic cells, and CDC25B-dependent cell cycle resumption in both oocytes and somatic cells. ..
  10. Funayama K, Murai F, Shimane M, Nomura H, Asano S. Adhesion-induced drug resistance in leukemia stem cells. Pharmacology. 2010;86:79-84 pubmed publisher
    ..These findings suggest that adhesion alone can lead to drug resistance in leukemic stem cells by various mechanisms. ..
  11. Narbonne Reveau K, Lilly M. The Cyclin-dependent kinase inhibitor Dacapo promotes genomic stability during premeiotic S phase. Mol Biol Cell. 2009;20:1960-9 pubmed publisher
    ..Finally, we report that dap(-/-) ovarian cysts frequently undergo an extramitotic division before meiotic entry, indicating that Dap influences the timing of the mitotic/meiotic transition. ..
  12. Ydenberg C, Rose M. Antagonistic regulation of Fus2p nuclear localization by pheromone signaling and the cell cycle. J Cell Biol. 2009;184:409-22 pubmed publisher
    ..Our results indicate a novel mechanism by which pheromone-induced proteins are regulated during the transition from mitosis to conjugation. ..
  13. Koon J, Kubiseski T. Developmental arrest of Caenorhabditis elegans BRAP-2 mutant exposed to oxidative stress is dependent on BRC-1. J Biol Chem. 2010;285:13437-43 pubmed publisher
    ..Our findings demonstrate that BRAP-2 is necessary for preventing an inappropriate response to elevated levels of reactive oxygen species by countering premature activation of BRC-1 and CKI-1. ..
  14. Choi S, Lee J, Jeong S, Im I, Lee S, Lee E, et al. 5,5'-substituted indirubin-3'-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity. J Med Chem. 2010;53:3696-706 pubmed publisher
    ..2-3.3 microM. A representative analogue, 3a, showed greater than 500-fold selectivity for CDK relative to selected kinase panel and potent in vivo anticancer activity. ..
  15. Mittag T, Marsh J, Grishaev A, Orlicky S, Lin H, Sicheri F, et al. Structure/function implications in a dynamic complex of the intrinsically disordered Sic1 with the Cdc4 subunit of an SCF ubiquitin ligase. Structure. 2010;18:494-506 pubmed publisher
    ..These results provide a physical picture of a protein that is predominantly disordered in both its free and bound states, enabling aspects of its structure/function relationship to be elucidated. ..
  16. Niculescu M, Yamamuro Y, Zeisel S. Choline availability modulates human neuroblastoma cell proliferation and alters the methylation of the promoter region of the cyclin-dependent kinase inhibitor 3 gene. J Neurochem. 2004;89:1252-9 pubmed
    ..This may be a mechanism for our previously reported observation that stem cell proliferation in hippocampus neuroepithelium is decreased in choline-deficient rat and mouse fetuses. ..
  17. Jiang H, Martin V, Gomez Manzano C, Johnson D, Alonso M, White E, et al. The RB-E2F1 pathway regulates autophagy. Cancer Res. 2010;70:7882-93 pubmed publisher
    ..Our findings indicate that RB induces autophagy by repressing E2F1 activity. We speculate that this newly discovered aspect of RB function is relevant to cancer development and therapy...
  18. Leitch A, Haslett C, Rossi A. Cyclin-dependent kinase inhibitor drugs as potential novel anti-inflammatory and pro-resolution agents. Br J Pharmacol. 2009;158:1004-16 pubmed publisher
    ..This review will discuss current understanding of the processes of inflammation and resolution but will focus on CDKis and their potential mechanisms of action. ..
  19. Byrne A, McLaren R, Mason P, Chai L, Dufault M, Huang Y, et al. Knockdown of human deubiquitinase PSMD14 induces cell cycle arrest and senescence. Exp Cell Res. 2010;316:258-71 pubmed publisher
    ..These data support the view that the 19S and 20S subunits of the proteasome have distinct biological functions and imply that targeting 19S and 20S would have distinct molecular consequences on tumor cells. ..
  20. Taniguchi D, Dai P, Hojo T, Yamaoka Y, Kubo T, Takamatsu T. Low-energy laser irradiation promotes synovial fibroblast proliferation by modulating p15 subcellular localization. Lasers Surg Med. 2009;41:232-9 pubmed publisher
    ..These insights may contribute to further investigation on biological effects and application of LELI in regenerative medicine. ..
  21. Yaakov G, Duch A, Garcia Rubio M, Clotet J, Jimenez J, Aguilera A, et al. The stress-activated protein kinase Hog1 mediates S phase delay in response to osmostress. Mol Biol Cell. 2009;20:3572-82 pubmed publisher
    ..The two mechanisms of Hog1 action lead to delayed firing of origins and prolonged replication, respectively. The Hog1-dependent delay of replication could be important to allow Hog1 to induce gene expression before replication. ..
  22. Monahan P, Rybak S, Raetzman L. The notch target gene HES1 regulates cell cycle inhibitor expression in the developing pituitary. Endocrinology. 2009;150:4386-94 pubmed publisher
  23. Borin T, Miyakawa A, Cardoso L, de Figueiredo Borges L, Gonçalves G, Krieger J. Apoptosis, cell proliferation and modulation of cyclin-dependent kinase inhibitor p21(cip1) in vascular remodelling during vein arterialization in the rat. Int J Exp Pathol. 2009;90:328-37 pubmed publisher
  24. Sugatani J, Osabe M, Kurosawa M, Kitamura N, Ikari A, Miwa M. Induction of UGT1A1 and CYP2B6 by an antimitogenic factor in HepG2 cells is mediated through suppression of cyclin-dependent kinase 2 activity: cell cycle-dependent expression. Drug Metab Dispos. 2010;38:177-86 pubmed publisher
  25. Weijers R. Risk loci for type 2 diabetes - quo vadis?. Clin Chem Lab Med. 2009;47:383-6 pubmed publisher
  26. Cho Y, Kim J, Yoon J, Cho S, Ko Y, Park J, et al. Constitutive activation of glycogen synthase kinase-3beta correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer. BMC Gastroenterol. 2010;10:91 pubmed publisher
    ..Thus, these findings suggest that GSK-3beta activation is a useful prognostic marker for the early-stage gastric cancer. ..
  27. Ohtani N, Mann D, Hara E. Cellular senescence: its role in tumor suppression and aging. Cancer Sci. 2009;100:792-7 pubmed publisher
    ..In this review, we discuss the mechanisms for cellular senescence and its roles in vivo. ..
  28. López Avilés S, Kapuy O, Novak B, Uhlmann F. Irreversibility of mitotic exit is the consequence of systems-level feedback. Nature. 2009;459:592-5 pubmed publisher
    ..Our findings demonstrate that the unidirectionality of mitotic exit is not the consequence of proteolysis but of systems-level feedback required to maintain the cell cycle in a new stable state. ..
  29. Hendy G, Kaji H, Canaff L. Cellular functions of menin. Adv Exp Med Biol. 2009;668:37-50 pubmed
    ..TGF-beta family members are key cytostatic molecules and menin is a facilitator of the transcriptional activity of their signaling molecules, the Smads, thereby ensuring appropriate control of cell proliferation and differentiation. ..
  30. Alvarado Moreno A, Chávez González A, Cerbulo A, Arriaga L, Mayani H. In vitro cell cycle dynamics of primitive hematopoietic cells from human umbilical cord blood. Hematology. 2010;15:11-20 pubmed publisher
  31. Kim S, Min H, Lee E, Kim Y, Bae K, Kang S, et al. Growth inhibition and cell cycle arrest in the G0/G1 by schizandrin, a dibenzocyclooctadiene lignan isolated from Schisandra chinensis, on T47D human breast cancer cells. Phytother Res. 2010;24:193-7 pubmed publisher
    ..These results suggest that schizandrin inhibits cell proliferation through the induction of cell cycle arrest with modulating cell cycle-related proteins in human breast cancer cells...
  32. LARREA M, Wander S, Slingerland J. p27 as Jekyll and Hyde: regulation of cell cycle and cell motility. Cell Cycle. 2009;8:3455-61 pubmed
    ..Further characterization of post-translational modifications governing p27 localization and its action on RhoA and the actin cytoskeleton may provide critical insights into human cancer metastasis. ..
  33. Boque N, Campion J, Milagro F, Moreno Aliaga M, Martinez J. Some cyclin-dependent kinase inhibitors-related genes are regulated by vitamin C in a model of diet-induced obesity. Biol Pharm Bull. 2009;32:1462-8 pubmed
    ..Thus, hepatic mRNA changes induced by ascorbic acid indicate a possible role of these genes in diet-induced oxidative stress processes. ..
  34. Kim H, Lee W, Lee S, Chae H, Kim D, Oh Y. Insulin-like growth factor binding protein-3 induces G1 cell cycle arrest with inhibition of cyclin-dependent kinase 2 and 4 in MCF-7 human breast cancer cells. Horm Metab Res. 2010;42:165-72 pubmed publisher
    ..Taken together, IGFBP-3 exerts its growth inhibitory action through not only induction of apoptosis but also the G1 cell cycle arrest in human breast cancer cells. ..
  35. Kuntz S, Kunz C, Rudloff S. Oligosaccharides from human milk induce growth arrest via G2/M by influencing growth-related cell cycle genes in intestinal epithelial cells. Br J Nutr. 2009;101:1306-15 pubmed publisher
    ..These results suggest that oligosaccharides from human milk inhibited intestinal cell proliferation and altered cell cycle dynamics by affecting corresponding regulator genes and mitogen-activated protein kinase signalling. ..
  36. Holdt L, Beutner F, Scholz M, Gielen S, Gäbel G, Bergert H, et al. ANRIL expression is associated with atherosclerosis risk at chromosome 9p21. Arterioscler Thromb Vasc Biol. 2010;30:620-7 pubmed publisher
    ..Our data provide robust evidence for an association of ANRIL but not CDKN2A, CDKN2B, C9orf53, and MTAP, with atherosclerosis and Chr9p21 genotype in a large cohort. ..
  37. Brocca S, Samalikova M, Uversky V, Lotti M, Vanoni M, Alberghina L, et al. Order propensity of an intrinsically disordered protein, the cyclin-dependent-kinase inhibitor Sic1. Proteins. 2009;76:731-46 pubmed publisher
    ..The mutations S201A and S201E, which are known to affect Sic1 function, do not have significant effects on the conformational properties of the pure protein. ..
  38. Jubelin G, Chavez C, Taïeb F, Banfield M, Samba Louaka A, Nobe R, et al. Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens. PLoS ONE. 2009;4:e4855 pubmed publisher
    ..These results reveal that Cif proteins form a growing family of cyclomodulins in bacteria that interact with very distinct hosts including insects, nematodes and humans. ..
  39. Cho H, Kwon H, Wang M. Expression of Kip-related protein 4 gene (KRP4) in response to auxin and cytokinin during growth of Arabidopsis thaliana. BMB Rep. 2010;43:273-8 pubmed
    ..Additionally, mitotic cyclins were up-regulated by NAA treatment. These results suggest that KRP4 as well as other cell cycle-related genes might contribute to the control of plant growth in response to exogenous hormones. ..
  40. Hu X, Shen H, Tian C, Yu H, Zheng G, XuFeng R, et al. Kinetics of normal hematopoietic stem and progenitor cells in a Notch1-induced leukemia model. Blood. 2009;114:3783-92 pubmed publisher
    ..It may also have important implications for cancer prevention and treatment in general. ..
  41. Hilliard N, Krahl D, Sellheyer K. p16 expression differentiates between desmoplastic Spitz nevus and desmoplastic melanoma. J Cutan Pathol. 2009;36:753-9 pubmed publisher
    ..The diagnostic conundrum occurs with confusion of desmoplastic melanoma with scars, hyalinizing blue nevi, desmoplastic Spitz nevi and diffuse neurofibromas...
  42. Buck S, Chiu D, Saito R. The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but distinct pathways to control cell cycle quiescence during C. elegans development. Cell Cycle. 2009;8:2613-20 pubmed
    ..Thus, both cki-1 and cki-2 mediate cell cycle quiescence, but our genetic and phenotypic analyses demonstrate that they act within distinct pathways to exert control over the cell cycle machinery. ..
  43. Kritsanida M, Magiatis P, Skaltsounis A, Peng Y, Li P, Wennogle L. Synthesis and antiproliferative activity of 7-azaindirubin-3'-oxime, a 7-aza isostere of the natural indirubin pharmacophore. J Nat Prod. 2009;72:2199-202 pubmed publisher
    ..7-Azaindirubin (10) and its 3'-oxime derivative (12) showed reduced activity as kinase inhibitors in comparison with other known indirubin derivatives, but antiproliferative activity with a best GI(50) value of 0.77 microM. ..
  44. Wu S, Ng L. Tocotrienols inhibited growth and induced apoptosis in human HeLa cells through the cell cycle signaling pathway. Integr Cancer Ther. 2010;9:66-72 pubmed publisher
  45. Bodson M, Breuskin I, Lefebvre P, Malgrange B. Hair cell progenitors: identification and regulatory genes. Acta Otolaryngol. 2010;130:312-7 pubmed publisher
    ..Characterization of signals that maintain, expand and regulate these progenitors will be essential for the biomedical application of stem cell populations to restore hearing. ..
  46. Liu Y, Sanoff H, Cho H, Burd C, Torrice C, Mohlke K, et al. INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis. PLoS ONE. 2009;4:e5027 pubmed publisher
  47. Yousafzai F, Al Kaff N, Moore G. Structural and functional relationship between the Ph1 locus protein 5B2 in wheat and CDK2 in mammals. Funct Integr Genomics. 2010;10:157-66 pubmed publisher
    ..Moreover, the Thr160/Tyr174 substitution is also accommodated by suitable alterations in the 3D space around Tyr174 and the 3D model of ( Ta ) 5B2 predicts Tyr174 to play the same role as Thr160 plays in CDK2. ..
  48. Freidkin I, Herman M, Tobar A, Chagnac A, Ori Y, Korzets A, et al. Effects of histone deacetylase inhibitors on rat mesangial cells. Am J Physiol Renal Physiol. 2010;298:F426-34 pubmed publisher
    ..Collectively, these data suggest a therapeutic potential for HDIs in the treatment of mesangial proliferative diseases and glomerulosclerosis. ..
  49. Spiller C, Wilhelm D, Koopman P. Retinoblastoma 1 protein modulates XY germ cell entry into G1/G0 arrest during fetal development in mice. Biol Reprod. 2010;82:433-43 pubmed publisher
    ..5 dpc, but in its absence, upregulation of other cell cycle suppressors, including Cdkn1b and Cdkn2b, can induce delayed germ cell arrest. ..
  50. Siller M, Anzenbacher P, Anzenbacherova E, Dolezal K, Popa I, Strnad M. Interactions of olomoucine II with human liver microsomal cytochromes P450. Drug Metab Dispos. 2009;37:1198-202 pubmed publisher
    ..The results indicate that use of olomoucine II as a drug could affect the activities of CYP3A4, CYP1A2, and CYP2C9 in vivo. Hence, the clinical relevance of these interactions should be carefully evaluated. ..