title: CARF (collaborator of ARF) interacts with HDM2: evidence for a novel regulatory feedback regulation of CARF-p53-HDM2-p21WAF1 pathway.
abstract: 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.
authors.affiliation: National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8562, Japan.
authors.forename: M Kamrul
authors.initials: MK
authors.lastname: Hasan
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yaguchi
authors.forename: Jun Itadani
authors.initials: JI
authors.lastname: Harada
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirano
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
mesh_terms: 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*
chemical_list: 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