Host cell factor-1 and E2F4 interact via multiple determinants in each protein.

Molecular and Cellular Biochemistry
Jozo KnezJohn P Capone

Abstract

Host Cell Factor (HCF-1) is a conserved, essential protein initially identified as a co-regulator for the Herpes Simplex Virus transactivator VP16. HCF-1 is variously involved in regulating transcription, splicing, cell proliferation and cytokinesis; however, its mechanisms of action remain unknown. HCF-1 function is manifested through an increasing assortment of cellular factors that target different regions of the protein. Several HCF-1 partners target the amino-terminal kelch domain of HCF-1 (residues 1-380) via a consensus HCF-binding motif (HBM) comprising the tetrapeptide (D/E)HXY. Searches of sequence databases indicated that this motif is present in E2F1 and E2F4, two members of the E2F family of cell cycle regulators. We show here that E2F4 specifically and directly interacts with HCF-1. Mutational analysis showed E2F4 independently targets the kelch domain and the basic domain (residues 450-902) of HCF-1, both of which are required for normal cell-cycle progression via separate determinants. The HBM-containing domain of E2F4 was necessary for interaction with the kelch domain of HCF-1 but not for interaction with the basic domain. Mutations in the HCF-1 kelch domain known to block cell growth abrogated E2F4 binding to...Continue Reading

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Citations

Sep 30, 2015·Molecular and Cellular Biology·Aurimas VinckeviciusDebabrata Chakravarti
Jul 10, 2012·Transcription·Zaffer Zargar, Shweta Tyagi
Oct 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jihye ParkJi-Joon Song
Jun 12, 2012·Nature Genetics·Samuel Peña-LlopisJames Brugarolas
Apr 28, 2017·Human Molecular Genetics·Anita M QuintanaTamim H Shaikh
Jun 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Aarthi NarayananThomas M Kristie
Mar 4, 2011·American Journal of Physiology. Cell Physiology·Camille W PaxtonJennifer M Pell
Aug 1, 2008·Journal of Virology·Gaelle Kolb, Thomas M Kristie
Jul 24, 2007·Molecular Cell·Angus C Wilson

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