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Molecular and Cellular Biology, February 2000, p. 919-928, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Mutations in Host Cell Factor 1 Separate Its Role
in Cell Proliferation from Recruitment of VP16 and LZIP
Shahana S.
Mahajan and
Angus C.
Wilson*
Department of Microbiology and Kaplan
Comprehensive Cancer Center, New York University School of
Medicine, New York, New York 10016
Received 8 September 1999/Returned for modification 13 October
1999/Accepted 1 November 1999
Host cell factor 1 (HCF-1) is a nuclear protein required for
progression through G1 phase of the cell cycle and, via its
association with VP16, transcriptional activation of the herpes simplex
virus immediate-early genes. Both functions require a six-bladed
-propeller domain encoded by residues 1 to 380 of HCF-1 as well as
an additional amino-terminal region. The
-propeller domain is well
conserved in HCF homologues, consistent with a critical cellular
function. To date, the only known cellular target of the
-propeller
is a bZIP transcription factor known as LZIP or Luman. Whether the interaction between HCF-1 and LZIP is required for cell proliferation remains to be determined. In this study, we used directed mutations to
show that all six blades of the HCF-1
-propeller contribute to
VP16-induced complex assembly, association with LZIP, and cell cycle
progression. Although LZIP and VP16 share a common tetrapeptide HCF-binding motif, our results reveal profound differences in their
interaction with HCF-1. Importantly, with several of the mutants we
observe a poor correlation between the ability to associate with LZIP
and promote cell proliferation in the context of the full HCF-1 amino
terminus, arguing that the HCF-1
-propeller domain must target other
cellular transcription factors in order to contribute to G1 progression.
*
Corresponding author. Mailing address: Department of
Microbiology, 550 First Ave., New York, NY 10016. Phone: (212)
263-0206. Fax: (212) 263-8276. E-mail:
wilsoa02{at}popmail.med.nyu.edu.
Molecular and Cellular Biology, February 2000, p. 919-928, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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