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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ARF gene (p19(ARF) in mouse and p14(ARF) in man) has become a central actor of the cell cycle regulation process as it participates to the ARF-MDM2-p53 pathway and the Rb-E2F-1 pathway. By use of immunoprecipitation and Western blotting (IP/WB), we now show that ARF physically associates with topoisomerase I (Topo I). ARF-Topo I immune complexes were detected in SF9 insect cells infected with recombinant baculoviruses encoding the two genes as well as in 293 cells that express endogenously these proteins. Preparations of a GST-ARF recombinant protein stimulated the DNA relaxation activity of Topo I but, in contrast, had no effect on the decatenation activity of Topo II. The Topo I stimulation was also detected in cell extracts of SF9 cells expressing both proteins. A confocal microscopy study indicated that part of ARF and Topo I colocalized in the granular component structure of the nucleolus. As a whole, our data indicate that Topo I is a new partner of ARF and suggest that ARF is involved in cell reactions that require Topo I.
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PMID:Human ARF protein interacts with topoisomerase I and stimulates its activity. 1131 11

We performed a yeast interactive screen in search of p19(ARF)-binding partners and have isolated a novel serine rich protein that is assigned to human chromosome 4q35 and mouse chromosome 8. The human and mouse proteins showed 84.2% homology. It is named CARF for its role as a putative Collaborator of ARF. CARF binds to both mouse and human ARF proteins. Its expression was detected in a variety of human tissues. The cDNA was expressed in bacteria and mammalian cells as a soluble and predominantly nucleoplasmic protein, respectively. CARF is a novel binding partner of ARF and might be involved in its p53-dependent or -independent tumor suppressive functions.
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PMID:A novel putative collaborator of p19ARF. 1258 88

CARF was first cloned as a novel binding partner of ARF from a yeast-interactive screen. CARF and ARF colocalize in the perinucleolar region and have a collaborative function. In the nucleoplasm, CARF interacts with p53 and enhances its function. We demonstrate that p53 downregulates CARF in a negative feedback regulatory loop and may also involve p53 antagonist HDM2.
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PMID:CARF regulates p19ARF-p53-p21WAF1 senescence pathway by multiple checkpoints. 1680 88

Replicative senescence, a major outcome of normal cells with finite lifespan, is a widely accepted in vitro model for ageing studies. Limited repair and defense mechanisms of normal cells, in addition to DNA alterations and oncogene inductions under stress, are believed to result in senescence as a protective mechanism to prevent undesirable proliferation of cells. The ARF/p53/p21(cip1/waf1) tumor suppression pathway acts as a molecular sensor and regulator of cellular stress, senescence, and immortalization. Understanding the molecular regulation of this pathway by intrinsic and extrinsic signals is extremely important to address unsolved questions in senescence and cancer. CARF was first discovered as a binding partner of ARF and has since been shown to have both ARF-dependent and -independent functions that converge to regulate p53 pathway. CARF directly binds to p53 and HDM2, and functions in a negative feedback pathway. Whereas CARF transcriptionally represses HDM2 to increase p53 activity, HDM2 in return degrades CARF. Thus, CARF may act as a novel key regulator of the p53 pathway at multiple checkpoints. The aim of this article is to discuss the current knowledge about functions of CARF and its impact on p53 pathway in regulation of senescence and carcinogenesis.
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PMID:CARF: an emerging regulator of p53 tumor suppressor and senescence pathway. 1855 16

Collaborator of ARF (CARF), initially identified as a binding partner of ARF (Alternate Reading Frame), has been shown to activate ARF-p53 pathway by multiple ways including stabilization of ARF and p53 tumor suppressor proteins, and transcriptional repression of a p53 antagonist, HDM2. Level of CARF expression was shown to determine fate of cells. Whereas its knockdown caused apoptosis, its over- and super-expressions caused senescence and increase in malignant properties of cancer cells, respectively, and were closely linked to increase and decrease in p53 activity. Using p53-compromised cancer cells, we demonstrate that CARF induces growth arrest when wild type p53 is present and in p53-absence, it promotes carcinogenesis. Biochemical analyses on CARF-induced molecular signaling revealed that in p53-null cells, it caused transcriptional repression of p21(WAF1) leading to increase in CDK4, CDK6, pRb and E2F1 resulting in continued cell cycle progression. Furthermore, it instigated increase in migration and invasion of cancer cells that was marked by upregulation of MMP2, MMP3, MMP9, uPA, several interleukins and VEGF expression. Consistent with these findings, we found that human clinical samples of epithelial and glial cancers (frequently marked by loss of p53 function) possessed high level of CARF expression showing a relationship with cancer aggressiveness. The data demonstrated that CARF could be considered as a diagnostic marker and a therapeutic target in p53-compromised malignancies.
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PMID:CARF (Collaborator of ARF) overexpression in p53-deficient cells promotes carcinogenesis. 2627 98

Rab-like protein 1 A (RBEL1A), which is a predominant isoform of RBEL1, has been identified to serve an important function in breast tumorigenesis and may be upregulated in breast tumor cells. RBEL1A may block the transcriptional activity of p53, which is important in the induction of cisplatin sensitivity. Previous studies supported the association between the induction of chemoresistance and the inhibition of p53 by RBEL1A. However, the response of RBEL1A to chemotreatment and its interaction with p53 remains to be investigated. The present study revealed that the cisplatin treatment induced the expression of RBEL1A in MCF-7 cells. Consistent with previous studies, the present study demonstrated that cisplatin treatment and RBEL1A overexpression blocked the oligomerization of p53 in MCF-7 cells and led to a decrease of the transcriptional activity of p53 and its downstream target gene p21. Additionally, upregulation of RBEL1A decreased the protein level of p53 by promoting the ubiquitination of p53. A cytotoxicity assay demonstrated that upregulation of RBEL1A partially contributed to chemosensitivity via inhibiting p53 in MCF-7 cells. A pG13L (p53-responsive reporter plasmid) luciferase reporter and co-immunoprecipitation assay revealed that upregulation of RBEL1A led to an inhibition of the transcriptional activity of p53 or its target gene p21. Analysis of cellular proliferation, cell cycle and invasion also confirmed the regulatory activity of RBEL1A on the malignancy of breast cancer cells. Taken together, these results suggest that the induction of RBEL1A following cisplatin treatment may partially inhibit chemosensitivity in a p53-dependent manner.
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PMID:Rab-like protein 1 A is upregulated by cisplatin treatment and partially inhibits chemoresistance by regulating p53 activity. 3019 76