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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Alternative reading frame protein (ARF)-independent function of CARF (collaborator of ARF) involves its interactions
Md Kamrul Hasan1, Tomoko Yaguchi, Yasumasu Minoda
1Gene Function Research Center, National Institute of Advanced Industrial Science & Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan.
Abstract:
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.
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