DIPA, which can localize to the centrosome, associates with p78/MCRS1/MSP58 and acts as a repressor of gene transcription.
DIPA (delta-interacting protein A) was initially identified as a protein that associates with the hepatitis delta antigen. In this study, we found that DIPA can associate with p78/MCRS/MSP58, a Forkhead-associated domain containing protein implicated in malignant transformation as well as in regulation of gene transcription and translation. We analyzed the interaction between DIPA and p78 by co-immunoprecipitation and identified the structural regions involved in the interaction. Consistent with the physical interaction, we found that DIPA is predominant co-localized with p78 to the nucleus. In addition, a fraction of DIPA can be detected on the centrosome. Furthermore, we demonstrate that DIPA can act as a repressor of gene transcription, an activity that appears to be enhanced by p78. Taken together, our results revealed a novel protein complex that plays a role in regulation of gene expression and cell proliferation. We propose that dysfunction of DIPA may contribute to malignant transformation by affecting the functions of p78.
Du
Xiulian
X
Department of Pathology and Laboratory Medicine, 252 John Morgan Building, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Wang
Qiang
Q
Hirohashi
Yoshihiko
Y
Greene
Mark I
MI
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; C101409:CCDC85B protein, human; D002352:Carrier Proteins; C113292:MCRS1 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins