Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - DUB-DECODE (Systematic Decoding of Deubiquitylase-Regulated Signaling Networks)

Teaser

The overall goal of the DUB-DECODE project is to understand how ubiquitylation, a type of protein modification, regulates function of proteins. In particular, we are interested in understanding the functions of deubiquitylases (DUBs) - the enzymes that remove ubiquitin that is...

Summary

The overall goal of the DUB-DECODE project is to understand how ubiquitylation, a type of protein modification, regulates function of proteins. In particular, we are interested in understanding the functions of deubiquitylases (DUBs) - the enzymes that remove ubiquitin that is conjugated to its substrates.

Work performed

Since the starting of the project, we have generated human cell line models to investigate DUB functions. In one of recently published paper, we identified a novel mechanism by which the deubiquitylase CYLD is recruited to tumor necrosis factor alpha (TNFa) receptor. TNFa is a key cytokine that functions in regulating innate immunity and inflammation. Binding of TNFa to its receptor can activate pro-survival signaling, or signaling that lead to cell death, and CYLD is implicated as a key regulator of these decisions. We showed that a novel protein SPATA2 constitutively binds to CYLD and recruits it to TNFa receptor, thus, serving a key role in determining the outcomes of TNFa receptor signaling.

Final results

Dysregulated TNFa signaling is implicated in human immune disorders, and understanding the mechanistic basis of TNFa will aid in designing improved therapeutic strategies for treating such disorders.