title: Interaction and functional cooperation of the cancer-amplified transcriptional coactivator activating signal cointegrator-2 and E2F-1 in cell proliferation.
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-kappaB, 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 G(1) 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.
authors.affiliation: Laboratory of Molecular Growth Regulation, National Institute of Health, Bethesda, MD, USA.
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Kong
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Yu
authors.forename: SunHwa
authors.initials: S
authors.lastname: Hong
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Won Gun
authors.initials: WG
authors.lastname: An
authors.forename: Jae Woon
authors.initials: JW
authors.lastname: Lee
authors.forename: JaeHun
authors.initials: J
authors.lastname: Cheong
mesh_terms: D000107:Acetylation; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D056918:Nuclear Receptor Coactivators; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C486559:NCOA6 protein, human; C405683:Ncoa6 protein, mouse; D056918:Nuclear Receptor Coactivators; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D008156:Luciferases