title: The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein.
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 PLZF in 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.
authors.affiliation: Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zürich, CH-8032 Zürich, Switzerland.
authors.forename: Patricia
authors.initials: P
authors.lastname: McLoughlin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ehler
authors.forename: Graeme
authors.initials: G
authors.lastname: Carlile
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Licht
authors.forename: Beat W
authors.initials: BW
authors.lastname: Schäfer
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020298:U937 Cells; D016335:Zinc Fingers
chemical_list: D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; C105987:FHL2 protein, human; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C092037:ZBTB16 protein, human; D005982:Glutathione Transferase