Identification of human dim1 as a peptidase with autocleavage activity.
Dim1 is a highly conserved splicing factor. It is encoded by an essential gene in fission yeast and the Caenorhabditis elegans. It may also be involved in tissue-specific or pathway-specific alternative splicing. Here, we report that besides its function in pre-mRNA splicing, human dim1 is a peptidase and has autocleavage activity. Its autocleavage results in a thioredoxin-like core that was shown previously to act as a dominant negative in fission yeast. The truncated form retains its peptidase activity. Future studies will be needed to identify residues important for dim1-peptidase activity and to characterize its substrate specificity. The biologic importance of dim1's peptidase function and its natural substrate(s) also need to be determined. However, if one or more of its substrates is involved in the pathogenesis of a human disease, dim1 may become a new target for drug development.
Jin
Tengchuan
T
Department of Biology, Illinois Institute of Technology, Chicago, IL 60616, USA.
Guo
Feng
F
Wang
Yingtong
Y
Zhang
Yu-Zhu
YZ
D002208:Caproates / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009842:Oligopeptides / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism*; D017415:Ribonucleoprotein, U5 Small Nuclear; D013879:Thioredoxins
D002208:Caproates; D018797:Cell Cycle Proteins; D009842:Oligopeptides; D017415:Ribonucleoprotein, U5 Small Nuclear; C506012:TXNL4A protein, human; C037652:hexanoic acid; D013879:Thioredoxins; C002101:chymostatin; D004492:Edetic Acid; D010447:Peptide Hydrolases