Interaction and Functional Cooperation of the Cancer-Amplified Transcriptional Coactivator Activating Signal Cointegrator-2 and E2F-1 in Cell Proliferation

Hee Jeong Kong, Hyun Jung Yu, Sun Hwa Hong, Min Jung Park, Young Hyun Choi, Won Gun An, Jae Woon Lee, Jae Hun Cheong

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Activating signal cointegrator-2 (ASC-2), a novel coactivator, is amplified in several cancer cells and known to interact with mitogenic transcription factors, including serum response factor, activating protein-1, and nuclear factor-κB, suggesting the physiological role of ASC-2 in the promotion of cell proliferation. Here, we show that the expression pattern of ASC-2 was correlated with that of E2F-1 for protein increases at G1 and S phase. Furthermore, cells stably overexpressing ASC-2 had an increased cell proliferation profile. These results prompted us to examine the functional interaction of ASC-2 and E2F-1. Biochemical evidence of protein interaction indicated that the transactivation domain of E2F-1 interacted with the COOH-terminal region of ASC-2. The importance of the E2F-1-ASC-2 interaction was supported by the demonstration that the coexpression of ASC-2 and E2F-1 synergistically transactivated E2F-1-driven gene transcription and the acetylation of E2F-1 protein was necessary for ASC-2-mediated transcriptional coactivation. Interestingly, overexpression of ASC-2 increased the endogenous protein level of E2F-1 in cells, resulting from the prolonged protein stability of E2F-1. Taken together, these results suggest that the cancer-amplified transcriptional coactivator ASC-2 may promote cell proliferation through enhancement of E2F-1-dependent transactivation of the expression of genes associated with cell cycle progression that may be available to favor tumor growth in vivo.

Original languageEnglish (US)
Pages (from-to)948-958
Number of pages11
JournalMolecular Cancer Research
Volume1
Issue number13
StatePublished - Nov 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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