Transcription regulation of caspase-1 by R393 of HIPPI and its molecular partner HIP-1.
Earlier we have shown that exogenous expression of HIPPI, a molecular partner of Huntingtin interacting protein HIP-1, induces apoptosis and increases expression of caspases-1, -8 and -10 in HeLa and Neuro2A cells. The C-terminal pseudo death effector domain of HIPPI (pDED-HIPPI) specifically interacts with the putative promoter sequences of these genes. In the present manuscript, we predict from structural modeling of pDED-HIPPI that R393 of HIPPI is important for such interaction. R393E mutation in pDED-HIPPI decreases the interaction with the putative promoter of caspase-1 in cells. Expression of caspase-1 is decreased in cells expressing mutant pDED-HIPPI in comparison to that observed in cells expressing wild type pDED-HIPPI. Using HIP-1 knocked down cells as well as over expressing HIP-1 with mutation at its nuclear localization signal and other deletion mutations, we demonstrate that translocation of HIPPI to the nucleus is mediated by HIP-1 for the increased expression of caspase-1. HIPPI-HIP-1 heterodimer is detected in cytoplasm as well as in the nucleus and is associated with transcription complex in cells. Taking together, we are able to show the importance of R393 of HIPPI and the role of HIPPI-HIP-1 heterodimer in the transcription regulation of caspase-1.
Banerjee
M
M
Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700 064, India.
Datta
M
M
Majumder
P
P
Mukhopadhyay
D
D
Bhattacharyya
N P
NP
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017209:Apoptosis; D020170:Caspase 1 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C073368:HIP1 protein, human; C499179:IFT57 protein, human; D004247:DNA; D020170:Caspase 1