Reciprocal regulation via protein-protein interaction between c-myc and p21cip1/waf1/sdi1 in DNA replication and transcription

被引:118
作者
Kitaura, H
Shinshi, M
Uchikoshi, Y
Ono, T
Tsurimoto, T
Yoshikawa, H
Iguchi-Ariga, SMM
Ariga, H
机构
[1] Hokkaido Univ, Grad Sch Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, Japan
[2] Hokkaido Univ, Coll Med Technol, Kita Ku, Sapporo, Hokkaido 0600812, Japan
[3] Nara Inst Sci & Technol, Fac Biol Sci, Nara 6300101, Japan
关键词
D O I
10.1074/jbc.275.14.10477
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The c-myc protooncogene product (c-Myc) is a transcription factor and is rapidly induced in resting cells following various mitogenic stimuli. c-Myc is thus suggested to play an important role in the transition from quiescence to proliferation. Despite numerous studies, including those on the connection between cyclin E/cyclin-dependent kinase 2 and c-Myc, little has been clarified about c-Myc in terms of the cell cycle regulation. Here we show that c-Myc can directly bind to the carboxyl-terminal region of the cyclin-dependent kinase inhibitor p(21cip1/waf1/sdi1) and thus partially relieves the p21 of the inhibitory effect on DNA synthesis directed by the proliferating cell nuclear antigen-dependent DNA polymerase delta. As for transcription, on the other hand, the p21 binding to the Myc box II region of c-Myc blocks c-Myc-Max complex formation on the E-box and thereby suppresses the transcriptional activation from the E-box by c-Myc. These results suggest that c-Myc activates DNA replication via inactivation of p21 and that p21, vice versa, represses the transcriptional activity of c-Myc. The balance of the reciprocal inactivation between c-Myc and p21 may determine the course of cellular processes such as cell proliferation, differentiation, and apoptosis.
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收藏
页码:10477 / 10483
页数:7
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