role of the hcf-1 basic region in sustaining cell proliferation角色hcf-1基本地区维持细胞增殖.pdfVIP

Role of the HCF-1 Basic Region in Sustaining Cell Proliferation Marco Mangone¤a, Michael P. Myers¤b, Winship Herr*¤c Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America Abstract Background: The human herpes simplex virus-associated host cell factor 1 (HCF-1) is a conserved human transcriptional co- regulator that links positive and negative histone modifying activities with sequence-specific DNA-binding transcription factors. It is synthesized as a 2035 amino acid precursor that is cleaved to generate an amino- (HCF-1N) terminal subunit, which promotes G1-to-S phase progression, and a carboxy- (HCF-1C) terminal subunit, which controls multiple aspects of cell division during M phase. The HCF-1N subunit contains a Kelch domain that tethers HCF-1 to sequence-specific DNA- binding transcription factors, and a poorly characterized so called ‘‘Basic’’ region (owing to a high ratio of basic vs. acidic amino acids) that is required for cell proliferation and has been shown to associate with the Sin3 histone deacetylase (HDAC) component. Here we studied the role of the Basic region in cell proliferation and G1-to-S phase transition assays. Methodology/Principal Findings: Surprisingly, much like the transcriptional activation domains of sequence-specific DNA- binding transcription factors, there is no unique sequence within the Basic region required for promoting cell proliferation or G1-to-S phase transition. Indeed, the ability to promote these activities is size dependent such that the shorter the Basic region segment the less activity observed. We find, however, that the Basic region requirements for promoting cell proliferation in a temperature-sensitive tsBN67 cell assay are more stringent than for G1-to-S phase progression in an HCF-1 siRNA-depletion HeLa-cel