Site-specific proteolysis of the transcriptional coactivator HCF-1 can regulate its interaction with protein cofactors.

Proceedings of the National Academy of Sciences of the United States of America
Jodi L Vogel, Thomas M Kristie

Abstract

Limited proteolytic processing is an important transcriptional regulatory mechanism. In various contexts, proteolysis controls the cytoplasmic-to-nuclear transport of important transcription factors or removes domains to produce factors with altered activities. The transcriptional coactivator host cell factor-1 (HCF-1) is proteolytically processed within a unique domain consisting of 20-aa reiterations. Site-specific cleavage within one or more repeats generates a family of amino- and carboxyl-terminal subunits that remain tightly associated. However, the consequences of HCF-1 processing have been undefined. In this study, it was determined that the HCF-1-processing domain interacts with several proteins including the transcriptional coactivator/corepressor four-and-a-half LIM domain-2 (FHL2). Analysis of this interaction has uncovered specificity with both sequence and context determinants within the reiterations of this processing domain. In cells, FHL2 interacts exclusively with the nonprocessed coactivator and costimulates transcription of an HCF-1-dependent target gene. The functional interaction of HCF-1 with FHL2 supports a model in which site-specific proteolysis regulates the interaction of HCF-1 with protein partners ...Continue Reading

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Citations

Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hua PengThomas M Kristie
Feb 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Salima DaouEl Bachir Affar
Aug 1, 2008·Journal of Virology·Gaelle Kolb, Thomas M Kristie
Aug 19, 2007·Molecular and Cellular Biology·Francesca CapotostiWinship Herr
Jun 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Aarthi NarayananThomas M Kristie
Feb 8, 2011·Cell·Francesca CapotostiWinship Herr
Oct 7, 2017·EMBO Reports·Jing ShenY Eugene Chin
Jan 10, 2021·Proceedings of the National Academy of Sciences of the United States of America·Zebulon G LevineSuzanne Walker
Mar 16, 2021·Molecular & Cellular Proteomics : MCP·Marissa MartinezNatasha E Zachara

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