Reciprocal regulation via protein-protein interaction between c-Myc and p21(cip1/waf1/sdi1) in DNA replication and transcription

Hirotake Kitaura, Minako Shinshi, Yasuko Uchikoshi, Takashi Ono, Toshiki Tsurimoto, Hiroshi Yoshikawa, Sanae M.M. Iguchi-Ariga, Hiroyoshi Ariga

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Abstract

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 p21(cip1/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 δ. 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.

Original languageEnglish
Pages (from-to)10477-10483
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number14
DOIs
Publication statusPublished - Apr 7 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Kitaura, H., Shinshi, M., Uchikoshi, Y., Ono, T., Tsurimoto, T., Yoshikawa, H., Iguchi-Ariga, S. M. M., & Ariga, H. (2000). Reciprocal regulation via protein-protein interaction between c-Myc and p21(cip1/waf1/sdi1) in DNA replication and transcription. Journal of Biological Chemistry, 275(14), 10477-10483. https://doi.org/10.1074/jbc.275.14.10477