Inhibition of LZIP-mediated transcription through direct interaction with a novel host cell factor-like protein.
Host cell factor 1 (HCF-1) is a cellular transcriptional coactivator which coordinates the assembly of enhancer complex through direct interactions with viral and cellular trans-activators such as VP16, Oct-1, LZIP, and GA-binding protein. These interactions are mediated by the beta-propeller domain comprising the first 380 residues of HCF-1 with six kelch repeats. Here we describe the identification and characterization of a novel HCF-like kelch repeat protein, designated HCLP-1. HCLP-1 is a ubiquitously expressed nuclear protein which is composed almost entirely of a six-bladed beta-propeller. HCLP-1 selectively interacts with LZIP but not with VP16. The physical interaction between HCLP-1 and LZIP leads to the repression of the LZIP-dependent transcription. The HCLP-1-binding domain of LZIP maps to residues 109-315, which contain the bZIP DNA-binding motif. Electrophoretic mobility shift assay demonstrates that HCLP-1 indeed interferes with the binding of LZIP to its DNA target. Thus, HCLP-1 serves a transcriptional co-repressor function mediated through its inhibitory interaction with the LZIP transcription factor. Our findings suggest a new mechanism for transcriptional regulation by HCF-like proteins.
Zhou
H J
HJ
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
Wong
C M
CM
Chen
J H
JH
Qiang
B Q
BQ
Yuan
J G
JG
Jin
D Y
DY
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D001665:Binding Sites; D017124:Conserved Sequence; D017362:Cyclic AMP Response Element-Binding Protein; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D051863:Host Cell Factor C1; D006801:Humans; D007700:Kinetics; D016350:Leucine Zippers; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D000951:Antigens, Neoplasm; C107941:CREB3 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; C497694:KLHDC2 protein, human; D011506:Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D004247:DNA; D008156:Luciferases