Alternative reading frame protein (ARF)-independent function of CARF (collaborator of ARF) involves its interactions with p53: evidence for a novel p53-activation pathway and its negative feedback control.
CARF, a collaborator of ARF (alternative reading frame protein), was cloned as a novel ARF-binding protein from a yeast-interaction screen. It potentiated ARF-mediated p53 function, and also caused a moderate increase in p53 activity in the absence of ARF. We herein report the molecular mechanism of ARF-independent function of CARF. By employing a variety of approaches, including overexpression of CARF, its suppression by small interfering RNA and use of protease inhibitors, we demonstrate that: (i) CARF directly interacts with wild-type p53, causing its stabilization and functional activation; and (ii) CARF and p53 levels show an inverse relationship that is instigated by a negative-feedback control via a proteasome-mediated degradation pathway.
Hasan
Md Kamrul
MK
Gene Function Research Center, National Institute of Advanced Industrial Science & Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan.
Yaguchi
Tomoko
T
Minoda
Yasumasu
Y
Hirano
Takashi
T
Taira
Kazunari
K
Wadhwa
Renu
R
Kaul
Sunil C
SC
D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D019556:COS Cells / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology*; D005347:Fibroblasts / Q000821:virology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology; D016364:Reading Frames / Q000235:genetics; D013539:Simian virus 40; D025803:Tumor Suppressor Protein p14ARF / Q000172:deficiency / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology
C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53