TAILIEUCHUNG - Báo cáo khoa học: Proteomic analysis reveals Hrs ubiquitin-interacting motif-mediated ubiquitin signaling in multiple cellular processes

Despite the critical importance of protein ubiquitination in the regulation of diverse cellular processes, the molecular mechanisms by which cells rec-ognize and transmit ubiquitin signals remain poorly understood. The endosomal sorting machinery component hepatocyte growth factor-regu-lated tyrosine kinase substrate (Hrs) contains a ubiquitin-interacting motif (UIM), which is believed to bind ubiquitinated membrane cargo proteins and mediate their sorting to the lysosomal degradation pathway. | Proteomic analysis reveals Hrs ubiquitin-interacting motif-mediated ubiquitin signaling in multiple cellular processes Julia W. Pridgeon Elizabeth A. Webber Di Sha Lian Li and Lih-Shen Chin Department of Pharmacology Emory University Schoolof Medicine Atlanta GA USA Keywords endocytic trafficking Hrs in vitro expression cloning ubiquitination ubiquitin-interacting motif Correspondence . Chin Department of Pharmacology Emory University Schoolof Medicine 1510 Clifton Road Atlanta GA 30322 USA Fax 1 404 727 0365 Tel 1 404 727 0361 E-mail chinl@ Website http These authors contributed equally to this work Received 26 June 2008 revised 19 October 2008 accepted 24 October 2008 doi Despite the critical importance of protein ubiquitination in the regulation of diverse cellular processes the molecular mechanisms by which cells recognize and transmit ubiquitin signals remain poorly understood. The endosomal sorting machinery component hepatocyte growth factor-regulated tyrosine kinase substrate Hrs contains a ubiquitin-interacting motif UIM which is believed to bind ubiquitinated membrane cargo proteins and mediate their sorting to the lysosomal degradation pathway. To gain insight into the role of Hrs UIM-mediated ubiquitin signaling in cells we performed a proteomic screen for Hrs UIM-interacting ubiquitinated proteins in human brain by using an in vitro expression cloning screening approach. We have identified 48 ubiquitinated proteins that are specifically recognized by the UIM domain of Hrs. Among them 12 are membrane proteins that are likely to be Hrs cargo proteins and four are membrane protein-associated adaptor proteins whose ubiquitination may act as a signal to target their associated membrane cargo for Hrs-mediated endosomal sorting. Other classes of the identified proteins include components of the vesicular trafficking machinery cell signaling molecules proteins associated with the .

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