Role of Jab1 in regulating Ubiquitin carboxy-terminal hydrolase-1 (UCHL1) activity

Mishra, P (2014) Role of Jab1 in regulating Ubiquitin carboxy-terminal hydrolase-1 (UCHL1) activity. Masters thesis, Indian Institute of Technology, Hyderabad.

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Abstract

UCH-L1 is a member of the ubiquitin C-terminal hydrolase (UCH) family of proteins that is expressed predominantly in neuronal tissues. Previous studies have shown that UCH-L1 is highly expressed in different types of cancers, suggesting a role in tumorigenesis. Currently, it is not clear how UCH-L1 activity is regulated in vivo. We hypothesized that enzymatic catalysis of UCH-L1 may allosterically be regulated by interacting proteins. A screen to identify UCH-L1 interacting protein revealed that JAB1/CSN-5, a COP-9 signalosome (CSN) subunit, to be the UCH-L1 interacting protein. The present study is aimed at understanding the role of Jab1 interaction on UCH-L1 activity. Jab1 is known to alter the activity of the other interacting protein either by phosphorylation or promote degradation by ubiquitin proteasome pathway. We performed UCHL1 activity assay on Ubiquitin substrate having C-terminal peptide extension and found that the presence of JAB1 in the assay is completely inhibiting UCHL1 deubiquitinase activity, without phosphorylation or ubiquitylation. Our results indicate a novel mode of regulation of UCHL1 activity by physical interaction with Jab1. The results from the present study will be helpful for further understanding of regulation of UCHL1 activity. It would also be of interest to see if similar mechanism exists for other UCH family and also will explore substrate specificity, stability and posttranslational modification of UCH-L1 in presence of Jab1. The outcome of this study may facilitate the design of drugs to treat cancers where UCH-L1 is overexpressed

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IITH Creators:
IITH CreatorsORCiD
Item Type: Thesis (Masters)
Uncontrolled Keywords: TD207
Subjects: Others > Biotechnology
Divisions: Department of Biotechnology
Depositing User: Users 4 not found.
Date Deposited: 01 Oct 2014 08:49
Last Modified: 08 Jul 2015 07:39
URI: http://raiith.iith.ac.in/id/eprint/70
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