title: Calpain is a signal transducer and activator of transcription (STAT) 3 and STAT5 protease.
abstract: Truncation of signal transducer and activator of transcription (STAT) 5 at the carboxy-terminal domain, either by genetic engineering or by proteolytic cleavage, results in generation of dominant-negative forms. A nuclear serine protease expressed in the myeloid precursor cells is known to mediate this cleavage, but other proteases responsible for this reaction were unknown. We found that calpain, a ubiquitously expressed cysteine protease, also trims STAT5 in vivo and in vitro, within the carboxy-terminal domain. Nuclear element is not necessary for calpain-mediated STAT5 cleavage, since this process occurs in platelets. We also found that STAT3 is a substrate for calpain in vivo and in vitro, indicating that calpain-mediated cleavage is a common feature of STAT3 and STAT5. Thus, our study reveals a novel pathway for posttranslational modification of STAT3 and STAT5.
authors.affiliation: Laboratory of Environmental Biology, Department of Preventive Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Oda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakao
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Fujita
mesh_terms: D001792:Blood Platelets / Q000201:enzymology; D002154:Calpain / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D008894:Milk Proteins; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D002154:Calpain; D003546:Cysteine Endopeptidases