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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, Polyomavirus Transforming / genetics
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Cloning, Molecular
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Glutathione Transferase / genetics
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Glutathione Transferase / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Humans
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Kruppel-Like Transcription Factors
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LIM-Homeodomain Proteins
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Promyelocytic Leukemia Zinc Finger Protein
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Recombinant Proteins / metabolism
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Repressor Proteins / metabolism*
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Saccharomyces cerevisiae / genetics
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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U937 Cells
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Zinc Fingers
Substances
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Antigens, Polyomavirus Transforming
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DNA-Binding Proteins
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FHL2 protein, human
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Homeodomain Proteins
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Kruppel-Like Transcription Factors
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LIM-Homeodomain Proteins
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Muscle Proteins
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Neoplasm Proteins
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Promyelocytic Leukemia Zinc Finger Protein
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Recombinant Proteins
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Repressor Proteins
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Transcription Factors
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ZBTB16 protein, human
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Glutathione Transferase