Genomes and Genes
cyclin dependent kinase inhibitor p21
Summary: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
- Havens C, Walter J. Docking of a specialized PIP Box onto chromatin-bound PCNA creates a degron for the ubiquitin ligase CRL4Cdt2. Mol Cell. 2009;35:93-104 pubmed publisher..Thus, CRL4(Cdt2) recognizes an unusual degron, which is assembled specifically on chromatin via the binding of a specialized PIP box to PCNA. ..
- Ye Y, Fu H, Zhou Y, DU C, Li B, Zhu L, et al. Study on the different expression of molecular markers between cardiac cancer and distal gastric cancer and their correlations with clinicopathological features. Dig Surg. 2009;26:384-91 pubmed publisher..Different molecular mechanisms may be involved in the tumorigenesis and development of cardiac cancer and distal gastric cancer. ..
- Park H, Choi S, Hong S, Hwang S, Park D. The ethyl acetate extract of Phellinus linteus grown on germinated brown rice induces G0/G1 cell cycle arrest and apoptosis in human colon carcinoma HT29 cells. Phytother Res. 2010;24:1019-26 pubmed publisher..linteus grown on PBR induces apoptosis accompanied by cell cycle arrest at G(0)/G(1) phase and regulates apoptosis-regulatory proteins, which may be applicable to anticancer therapy. ..
- Nakahata S, Yamazaki S, Nakauchi H, Morishita K. Downregulation of ZEB1 and overexpression of Smad7 contribute to resistance to TGF-beta1-mediated growth suppression in adult T-cell leukemia/lymphoma. Oncogene. 2010;29:4157-69 pubmed publisher..Altogether, these results suggest that both ZEB1 downregulation and Smad7 overexpression contribute to resistance to TGF-beta1-mediated growth suppression in ATLL. ..
- Park J, Sun X, Roeder R. The SANT domain of p400 ATPase represses acetyltransferase activity and coactivator function of TIP60 in basal p21 gene expression. Mol Cell Biol. 2010;30:2750-61 pubmed publisher..Z at the promoter. ..
- Schwer C, Mutschler M, Stoll P, Goebel U, Humar M, Hoetzel A, et al. Carbon monoxide releasing molecule-2 inhibits pancreatic stellate cell proliferation by activating p38 mitogen-activated protein kinase/heme oxygenase-1 signaling. Mol Pharmacol. 2010;77:660-9 pubmed publisher..Taken together, our results suggest that CORM-2 inhibits PSC proliferation by activation of the p38/HO-1 pathway. These findings may indicate a therapeutic potential of CO carriers in the treatment of pancreatic fibrosis. ..
- Jung Y, Qian Y, Chen X. Examination of the expanding pathways for the regulation of p21 expression and activity. Cell Signal. 2010;22:1003-12 pubmed publisher..This review will briefly discuss the activity of p21 and focus on current knowledge of the determinants that control p21 transcription, mRNA stability and translation, and protein stability and activity. ..
- Gonzalez Sarrias A, Giménez Bastida J, García Conesa M, Gómez Sánchez M, García Talavera N, Gil Izquierdo A, et al. Occurrence of urolithins, gut microbiota ellagic acid metabolites and proliferation markers expression response in the human prostate gland upon consumption of walnuts and pomegranate juice. Mol Nutr Food Res. 2010;54:311-22 pubmed publisher..Our results suggest that urolithin glucuronides and dimethyl ellagic acid may be the molecules responsible for the beneficial effects of PJ against PCa...
- Chen Z, Cai L, Bie P, Wang S, Jiang Y, Dong J, et al. Roles of Fyn in pancreatic cancer metastasis. J Gastroenterol Hepatol. 2010;25:293-301 pubmed publisher..Our results suggest a possible mechanism by which Fyn activity regulates cell proliferation and apoptosis that exerts an effect on pancreatic cancer metastasis. ..
- Cao X, Wang A, Jiao R, Wang C, Mao D, Yan L, et al. Surfactin induces apoptosis and G(2)/M arrest in human breast cancer MCF-7 cells through cell cycle factor regulation. Cell Biochem Biophys. 2009;55:163-71 pubmed publisher..The mechanism which surfactin caused G(2)/M arrest seems to be through cell cycle factor regulation. ..
- Banach Orlowska M, Pilecka I, Torun A, Pyrzynska B, Miaczynska M. Functional characterization of the interactions between endosomal adaptor protein APPL1 and the NuRD co-repressor complex. Biochem J. 2009;423:389-400 pubmed publisher..In a broader sense, these results contribute to an emerging theme of endocytic proteins playing alternative roles in the cell nucleus. ..
- Guo J, Chintharlapalli S, Lee S, Cho S, Lei P, Papineni S, et al. Peroxisome proliferator-activated receptor gamma-dependent activity of indole ring-substituted 1,1-bis(3'-indolyl)-1-(p-biphenyl)methanes in cancer cells. Cancer Chemother Pharmacol. 2010;66:141-50 pubmed publisher..The results demonstrate that DIM-C-pPhC(6)H(5) and indole ring-substituted analogs are selective PPARgamma modulators. ..
- Xu Y, Chen Q, Li W, Su X, Chen T, Liu Y, et al. Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness. Oncogene. 2010;29:3386-97 pubmed publisher..Therefore, AIB1 is a master regulator of human HCC growth and might be a useful molecular target for HCC prognosis and treatment. ..
- West L, Roy S, Lachmi Weiner K, Hayashi R, Shi X, Appella E, et al. The MBT repeats of L3MBTL1 link SET8-mediated p53 methylation at lysine 382 to target gene repression. J Biol Chem. 2010;285:37725-32 pubmed publisher..Together, we identify L3MBTL1 as the second known methyl-p53 effector protein, and provide a molecular explanation for the mechanism by which p53K382me1 is transduced to regulate p53 activity. ..
- Alaoui El Azher M, Mans J, Baker H, Chen C, Progulske Fox A, Lamont R, et al. Role of the ATM-checkpoint kinase 2 pathway in CDT-mediated apoptosis of gingival epithelial cells. PLoS ONE. 2010;5:e11714 pubmed publisher..This model potentially explains conflicting reports on the biological activity of the A. actinomycetemcomitans CDT. ..
- Xu J, Dang Y, Ren Y, Liu J. Cholesterol trafficking is required for mTOR activation in endothelial cells. Proc Natl Acad Sci U S A. 2010;107:4764-9 pubmed publisher..These observations suggest that mTOR is likely to be involved in sensing membrane sterol concentrations in endothelial cells, and the cholesterol trafficking pathway is a promising target for the discovery of inhibitors of angiogenesis. ..
- Owen H, Ahmed S, Farquharson C. Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo. Calcif Tissue Int. 2009;85:326-34 pubmed publisher..These findings suggest that p21 does not directly contribute to GC-induced growth retardation in vivo but is involved in the maintenance of the growth plate. ..
- Acharya S, Chatterjee S, Kumar P, Bhattacharjee M, Chaudhuri S, Chaudhuri S. Induction of G1 arrest in glioma cells by T11TS is associated with upregulation of Cip1/Kip1 and concurrent downregulation of cyclin D (1 and 3). Anticancer Drugs. 2010;21:53-64 pubmed publisher..Thus, our observations have uncovered an antiproliferative pathway for T11TS, causing retardation of glioma cell cycle...
- Lim S, Janzer A, Becker A, Zimmer A, Schüle R, Buettner R, et al. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis. 2010;31:512-20 pubmed publisher..In summary, our data indicate that LSD1 may provide a predictive marker for aggressive biology and a novel attractive therapeutic target for treatment of ER-negative breast cancers. ..
- Lu X, Chen D, Liu Z, Li C, Liu Y, Zhou J, et al. Enhanced survival in vitro of human corneal endothelial cells using mouse embryonic stem cell conditioned medium. Mol Vis. 2010;16:611-22 pubmed..These effects may be achieved through inhibition of p21 expression and apoptosis. These results suggested that 25%ESC-CM may be a new tool for cultivating HCECs for transplantation. ..
- Heyne K, Willnecker V, Schneider J, CONRAD M, Raulf N, Schüle R, et al. NIR, an inhibitor of histone acetyltransferases, regulates transcription factor TAp63 and is controlled by the cell cycle. Nucleic Acids Res. 2010;38:3159-71 pubmed publisher..Thus, NIR is a cell-cycle-controlled, novel negative regulator of TAp63. The low levels of nucleoplasmic NIR might act as a buffer toward potentially toxic TAp63. ..
- Li M, Li Z, Sun X, Yang L, Fang P, Liu Y, et al. Heme oxygenase-1/p21WAF1 mediates peroxisome proliferator-activated receptor-gamma signaling inhibition of proliferation of rat pulmonary artery smooth muscle cells. FEBS J. 2010;277:1543-50 pubmed publisher..Our study also indicates that rosiglitazone, a medicine widely used in the treatment of type 2 diabetes mellitus, has potential benefits for patients with pulmonary hypertension...
- Jagelska E, Pivonkova H, Fojta M, Brazda V. The potential of the cruciform structure formation as an important factor influencing p53 sequence-specific binding to natural DNA targets. Biochem Biophys Res Commun. 2010;391:1409-14 pubmed publisher..Not only the appearance of the cruciform structures within naked supercoiled DNA, but also the potential of the binding sites for adopting the non-B structures can contribute to a more favorable p53-DNA complex. ..
- Taghavi N, Biramijamal F, Abbaszadegan M, Khademi H, Sotoudeh M, Khoshbakht S. P21(waf1/cip1) gene polymorphisms and possible interaction with cigarette smoking in esophageal squamous cell carcinoma in northeastern Iran: a preliminary study. Arch Iran Med. 2010;13:235-42 pubmed..However, their interaction with cigarette smoking may influence the susceptibility to ESCC development in northeastern Iran. ..
- Zemskova M, Lilly M, Lin Y, Song J, Kraft A. p53-dependent induction of prostate cancer cell senescence by the PIM1 protein kinase. Mol Cancer Res. 2010;8:1126-41 pubmed publisher..Based on these results, PIM1 will have its most profound effects on tumorigenesis in situations where the senescence response is inactivated. ..
- Ota K, Matsumiya T, Sakuraba H, Imaizumi T, Yoshida H, Kawaguchi S, et al. Interferon-alpha2b induces p21cip1/waf1 degradation and cell proliferation in HeLa cells. Cell Cycle. 2010;9:131-9 pubmed..These results provide a novel role of Type I IFNs in cell cycle regulation and may define an importance of individualized IFN-based therapy against specific types of cancer. ..
- Lou Z, Wei J, Riethman H, Baur J, Voglauer R, Shay J, et al. Telomere length regulates ISG15 expression in human cells. Aging (Albany NY). 2009;1:608-21 pubmed..The upregulation of ISG15 with telomere shortening may contribute to chronic inflammatory states associated with human aging. ..
- Huang C, Lo C, Chiu C, Shyur L. Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice. Br J Pharmacol. 2010;159:856-71 pubmed publisher..Our data provide evidence for the suppression of mammary adenocarcinoma by DET with several mechanisms and suggest that DET has potential as a chemopreventive agent for breast cancer. ..
- Kang J, Kim J, Jang S, Bae Y. The p53-p21(Cip1/WAF1) pathway is necessary for cellular senescence induced by the inhibition of protein kinase CKII in human colon cancer cells. Mol Cells. 2009;28:489-94 pubmed publisher..Taken together, this study shows that the activation of the p53-p21(Cip1/WAF1) pathway acts as a major mediator of cellular senescence induced by CKII inhibition. ..
- Nakamura S, Hirano I, Okinaka K, Takemura T, Yokota D, Ono T, et al. The FOXM1 transcriptional factor promotes the proliferation of leukemia cells through modulation of cell cycle progression in acute myeloid leukemia. Carcinogenesis. 2010;31:2012-21 pubmed publisher..Thus, inhibition of FOXM1 expression represents an attractive target for AML therapy. ..
- Heminger K, Markey M, Mpagi M, Berberich S. Alterations in gene expression and sensitivity to genotoxic stress following HdmX or Hdm2 knockdown in human tumor cells harboring wild-type p53. Aging (Albany NY). 2009;1:89-108 pubmed..Taken together, these results provide novel insights into the reactivation of p53 in cells overexpressing HdmX and Hdm2. ..
- Kim Y, Oh K, Park R, Xuan N, Kang T, Kwon D, et al. HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling. Mol Cancer. 2010;9:124 pubmed publisher..These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling. ..
- Noro R, Miyanaga A, Minegishi Y, Okano T, Seike M, Soeno C, et al. Histone deacetylase inhibitor enhances sensitivity of non-small-cell lung cancer cells to 5-FU/S-1 via down-regulation of thymidylate synthase expression and up-regulation of p21(waf1/cip1) expression. Cancer Sci. 2010;101:1424-30 pubmed publisher..We conclude that combination therapy with SAHA and S-1 in lung cancer may be promising due to its potential to overcome S-1 resistance via modulation of 5-FU/S-1 sensitivity-associated biomarker (TS) by HDAC inhibitor. ..
- Vucetic Z, Totoki K, Schoch H, Whitaker K, Hill Smith T, Lucki I, et al. Early life protein restriction alters dopamine circuitry. Neuroscience. 2010;168:359-70 pubmed publisher..This animal model, with both face validity (behavior) and construct validity (link to IUGR and dopamine dysfunction) may prove useful in identifying underlying mechanisms linking IUGR and adverse neurobehavioral outcomes such as ADHD. ..
- Jeong J, Ju S, Park J, Lee J, Yun K, Kwon S, et al. Antioxidant activity in essential oils of Cnidium officinale makino and Ligusticum chuanxiong Hort and their inhibitory effects on DNA damage and apoptosis induced by ultraviolet B in mammalian cell. Cancer Epidemiol. 2009;33:41-6 pubmed publisher..These results suggest that essential oils in C. officinale and L. chuanxiong may exert inhibitory effects on DNA damage and apoptosis induced by UVB through their high free radical scavenging ability. ..
- Ma X, Jin Y, Miao Q, Li S, He Y, Lv H. Histone deacetylase inhibitor trichostatin A modulates cell cycles in A2780 human ovarian cancer cell lines. Eur J Gynaecol Oncol. 2009;30:263-6 pubmed..TSA causes A2780 cell blockage in the G2/M phase and inhibits cell proliferation of A2780 cells. The minimum level of active TSA is 100 nM and the minimum time is 12 hours. The effect relies on time and concentration. ..
- Roh J, Kim B, Lee C, Kim J, Chung H, Kim J, et al. P53 codon 72 and p21 codon 31 polymorphisms and susceptibility to cervical adenocarcinoma in Korean women. Oncol Res. 2010;18:453-9 pubmed..22; 95% CI 2.24-12.16), although the interaction of the two genes could not be found. These significant differences were intensified in groups with high-risk HPV infection (types 16 or 18). ..
- Matsuu Matsuyama M, Nakashima M, Shichijo K, Okaichi K, Nakayama T, Sekine I. Basic fibroblast growth factor suppresses radiation-induced apoptosis and TP53 pathway in rat small intestine. Radiat Res. 2010;174:52-61 pubmed publisher..The inhibition of apoptosis thus might be related to suppression of the TP53 pathway. ..
- Iwatani K, Fujimoto T, Ito T. Cyclin D1 blocks the anti-proliferative function of RUNX3 by interfering with RUNX3-p300 interaction. Biochem Biophys Res Commun. 2010;400:426-31 pubmed publisher..Since RUNX3 plays tumor suppressive roles in a wide range of cancers, a non-canonical cyclin D1 function may be critical for neoplastic transformation of the epithelial cells in which RUNX3 regulates proliferation. ..
- Liu T, Wu S, Huang M, Lo F, Tsai M, Tsai C, et al. EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis. Mol Cancer. 2010;9:32 pubmed publisher..The anti-apoptotic activity of EBER1 may be important in the rescue of Reed-Sternberg cells from drug-induced apoptosis and in the clinical behaviors of EBV+ HLs. ..
- Tan Y, Chen Y, Yu L, Zhu H, Meng X, Huang X, et al. Two-fold elevation of expression of FoxM1 transcription factor in mouse embryonic fibroblasts enhances cell cycle checkpoint activity by stimulating p21 and Chk1 transcription. Cell Prolif. 2010;43:494-504 pubmed publisher..ChIP, EMSA and cotransfection assays confirmed that FoxM1 stimulated promoters of p21 and Chk1. Chk1 and p21 are direct transcription targets of FoxM1 and FoxM1 participates in transcriptional responses to stress in normal cells. ..
- Kasai H, Nakashima K, Yokota M, Nishihara T. The G1 cell cycle arrest of macrophages infected with Aggregatibacter actinomycetemcomitans. Oral Dis. 2010;16:305-9 pubmed publisher..These findings suggest that cyclin D1 and D2 and p21(CIP1/WAF1) participate in G1 cell cycle arrest in A. actinomycetemcomitans-infected J774.1 cells. ..
- Lei D, Sturgis E, Liu Z, Zafereo M, Wei Q, Li G. Genetic polymorphisms of p21 and risk of second primary malignancy in patients with index squamous cell carcinoma of the head and neck. Carcinogenesis. 2010;31:222-7 pubmed publisher..00, 95% CI = 1.26-3.00), and the risk was particularly pronounced in several subgroups. Our results support an increased risk of SPM after index SCCHN with both p21 polymorphisms individually and in combination...
- Geng M, Wang L, Cao Y, Li H, Liu X. [Relationship of the expression of cyclin D1 and P21WAF1 with the sensitivity to chemotherapeutic drugs on gastric cancers]. Zhonghua Wei Chang Wai Ke Za Zhi. 2009;12:615-7 pubmed..Expression of cyclin D1 and P21WAF1 is related with drug-resistance of tumor. Examination of cyclinD1 and P21WAF1 would have reference value in selection of chemotherapeutic drugs. ..
- Mirzayans R, Andrais B, Scott A, Paterson M, Murray D. Single-cell analysis of p16(INK4a) and p21(WAF1) expression suggests distinct mechanisms of senescence in normal human and Li-Fraumeni Syndrome fibroblasts. J Cell Physiol. 2010;223:57-67 pubmed publisher..The possibility that one of the tumor-suppressor functions of p16 may be associated with genomic instability, preventing the emergence of malignant progeny from polyploid giant cells, is also supported by these results. ..