CARF (collaborator of ARF) interacts with HDM2: evidence for a novel regulatory feedback regulation of CARF-p53-HDM2-p21WAF1 pathway.
We initially cloned CARF (collaborator of ARF), as a novel ARF-binding protein by a yeast interaction screen. It also interacts with p53 directly leading to ARF-independent enhancement of p53 function and in turn undergoes a negative feedback regulation. Herein we report that i) CARF interacts with HDM2 and undergoes degradation ... by an HDM2-dependent proteasome pathway, and ii) it acts as a transcriptional repressor of HDM2. By overexpression and silencing studies, we demonstrated that CARF exerts a vital control on the p53-HDM2-p21WAF1 pathway that is frequently altered in cancer cells.
Mesh Terms:
Cyclin-Dependent Kinase Inhibitor p21, Feedback, Physiological, Gene Expression Regulation, HCT116 Cells, HeLa Cells, Humans, Models, Biological, Protein Binding, Proto-Oncogene Proteins c-mdm2, Repressor Proteins, Signal Transduction, Transcription Factors, Tumor Cells, Cultured, Tumor Suppressor Protein p14ARF, Tumor Suppressor Protein p53
Cyclin-Dependent Kinase Inhibitor p21, Feedback, Physiological, Gene Expression Regulation, HCT116 Cells, HeLa Cells, Humans, Models, Biological, Protein Binding, Proto-Oncogene Proteins c-mdm2, Repressor Proteins, Signal Transduction, Transcription Factors, Tumor Cells, Cultured, Tumor Suppressor Protein p14ARF, Tumor Suppressor Protein p53
Int. J. Oncol.
Date: Mar. 01, 2008
PubMed ID: 18292944
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