Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter

Monica Di Padova, Tiziana Bruno, Francesca De Nicola, Simona Iezzi, Carmen D'Angelo, Rita Gallo, Daniela Nicosia, Nicoletta Corbi, Annamaria Biroccio, Aristide Floridi, Claudio Passananti, Maurizio Fanciulli

Research output: Contribution to journalArticle

Abstract

Che-1 is a recently identified human RNA polymerase II binding protein involved in the regulation of gene transcription and cell proliferation. We previously demonstrated that Che-1 inhibits the Rb growth-suppressing function by interfering with Rb-mediated HDAC1 recruitment on E2F target gene promoters. By hybridization of cancer profile arrays, we found that Che-1 expression is strongly down-regulated in several tumors, including colon and kidney carcinomas, compared with the relative normal tissues. Consistent with these data, Che-1 overexpression inhibits proliferation of HCT116 and LoVo human colon carcinoma cell lines by activation of the cyclin-dependent kinase inhibitor p21WAF1/Cip1 in a p53-independent manner and by promoting growth arrest at the G1 phase of the cell cycle. Che-1 activates p21WAF1/Cip1 by displacing histone deacetylase (HDAC)1 from the Sp1 binding sites of the p21WAF1/Cip1 gene promoter and accumulating acetylated histone H3 on these sites. Accordingly, Che-1-specific RNA interference negatively affects p21WAF1/Cip1 transactivation and increases cell proliferation in HCT116 cells. Taken together, our results indicate that Che-1 can be considered a general HDAC1 competitor and its down-regulation is involved in colon carcinoma cell proliferation.

Original languageEnglish
Pages (from-to)36496-36504
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number38
DOIs
Publication statusPublished - Sep 19 2003

ASJC Scopus subject areas

  • Biochemistry

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    Di Padova, M., Bruno, T., De Nicola, F., Iezzi, S., D'Angelo, C., Gallo, R., Nicosia, D., Corbi, N., Biroccio, A., Floridi, A., Passananti, C., & Fanciulli, M. (2003). Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter. Journal of Biological Chemistry, 278(38), 36496-36504. https://doi.org/10.1074/jbc.M306694200