The LIM-only Protein DRAL/FHL2 Interacts with and Is a Corepressor for the Promyelocytic Leukemia Zinc Finger Protein*
- From the Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zürich, CH-8032 Zürich, the ‡Institute of Cell Biology, ETH Hönggerberg, 8093 Zürich, Switzerland, and the§Department of Medicine, The Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029
Abstract
Members of the four-and-a-half-LIM domain (FHL) protein family, which are expressed in a tissue- and stage-specific manner, have been reported previously to function as transcriptional coactivators. One of these is the p53-inducible protein DRAL/FHL2 (where DRAL is down-regulated in rhabdomyosarcoma LIM domain protein). In this work, we identified potential binding partners for DRAL/FHL2 using an inducible yeast two-hybrid system. We present evidence of a functional interaction between the promyelocytic leukemia zinc finger protein (PLZF) and DRAL/FHL2. PLZF is a sequence-specific transcriptional repressor whose function relies on recruitment of corepressors that form part of the histone deacetylase complex involved in chromatin remodeling. DRAL/FHL2 interacts specifically with PLZFin vitro and in vivo and augments transcriptional repression mediated by PLZF. This is the first reported incidence of a bona fide FHL protein-mediated corepression and supports the notion of these proteins having a role as coregulators of tissue-specific gene expression.
Footnotes
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↵* This work was supported by grants from the Krebsforschung Schweiz, the Krebsliga of Kt. Zug, Swiss National Science Foundation Grant 31-56869.99 (to B. W. S.), National Institutes of Health Grant R01 CA59936, and American Cancer Society Award DHP 160 (to J. D. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ To whom correspondence should be addressed. Tel.: 41-1-266-7553; Fax: 41-1-266-7169; E-mail: schafer@kispi.unizh.ch.
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Published, JBC Papers in Press, July 26, 2002, DOI 10.1074/jbc.M203336200
- Abbreviations:
- NCoR
-
nuclear receptor corepressor
- HDAC
-
histone deacetylase
- FHL
-
four-and-a-half-LIM domain protein
- PLZF
-
promyelocytic leukemia zinc finger protein
- DRAL
-
down-regulated in rhabdomyosarcoma LIM domain protein
- ACT
-
activator of CREM in testis
- GST
-
glutathioneS-transferase
- DNA-BD
-
DNA-binding domain
- FCS
-
fetal calf serum
- AD
-
activation domain
- IVT
-
in vitro translated
- CREM
-
cAMP-responsive element modulator
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- Received April 8, 2002.
- Revision received June 20, 2002.
- The American Society for Biochemistry and Molecular Biology, Inc.
