Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 9 May 2006
Vol. 2006, Issue 334, p. tw158
[DOI: 10.1126/stke.3342006tw158]

EDITORS' CHOICE

TRANSCRIPTION Site for Proteolysis and Protein Interaction

HCF-1 (host cell factor-1) is a transcriptional coactivator that is involved in the stimulation of various mammalian genes, as well as the immediate early (IE) genes of herpes simplex virus. HCF-1 interacts with multiple transcriptional regulators and is autocatalytically processed within the nucleus to generate a family of polypeptides that remain associated. Vogel and Kristie showed (using yeast two-hybrid and glutathione S-transferase pull-down experiments) that HCF-1 interacted with the transcriptional regulator four-and-a-half LIM domain-2 (FHL2) through specific regions of the proteolytic processing domain (PPD) of HCF-1. Furthermore, the interaction appeared to be specific for FHL2, because other proteins with LIM domains either did not interact or interacted only weakly. FHL2 preferentially interacted with the noncleaved form of HCF-1, and in a reporter gene assay, a noncleavable mutant of HCF-1 was substantially more effective at stimulating FHL2-dependent gene expression than was the wild-type HCF-1. Thus, in terms of the interaction with FHL2, proteolysis of HCF-1 may serve as a negative regulatory mechanism. However, whether and how HCF-1 autocatalysis is regulated remains to be determined. A reporter gene assay for two different IE gene promoters indicated that FHL2 stimulated expression of those genes in a dose-dependent manner, thereby implicating FHL2 in herpes virus infection.

J. L. Vogel, T. M. Kristie, Site-specific proteolysis of the transcriptional coactivator HCF-1 can regulate its interaction with protein cofactors. Proc. Natl. Acad. Sci. U.S.A. 103, 6817-6822 (2006). [Abstract] [Full Text]

Citation: Site for Proteolysis and Protein Interaction. Sci. STKE 2006, tw158 (2006).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882