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.
Hasan
M Kamrul
MK
National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8562, Japan.
Yaguchi
Tomoko
T
Harada
Jun Itadani
JI
Hirano
Takashi
T
Wadhwa
Renu
R
Kaul
Sunil C
SC
D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism* / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012097:Repressor Proteins; D014157:Transcription Factors; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2