Sign up for Table of Contents Alerts.

Email this page

Print this page

Reports

U-box-type ubiquitin E4 ligase, UFD2a attenuates cisplatin mediated degradation of ΔNp63α

Aditi Chatterjee, Sunil Upadhyay, Xiaofei Chang, Jatin K. Nagpal, Barry Trink and David Sidransky

Purchase article for $19

Subscribe to this journal for $129/year

ΔNp63α, the dominant negative isoform of the p63 family is an essential survival factor in head and neck squamous cell carcinoma. This isoform has been shown to be down regulated in response to several DNA damaging agents, including cisplatin. But little is understood about the post-translational protein stability of ΔNp63α. In this present study we demonstrate for the first time that ΔNp63α physically interacts with U-box-type E4 ubiquitin ligase UFD2a. UFD2a stabilizes ΔNp63α, and ubiquitylation of ΔNp63α is attenuated by UFD2a both in the presence and absence of cisplatin. Ectopic expression of UFD2a increased the half-life of ΔNp63α in association with a significant enhancement of the repressive transcriptional activity of ΔNp63α. Downregulation of endogenous UFD2a by RNAi resulted in degradation of ΔNp63α. Taken together, our current study provides an insight onto the regulation of ΔNp63α protein levels in response to cisplatin and also suggests that UFD2a might play an important role in the regulation of cisplatin mediated cell death mediated by p63.

Authors

Aditi Chatterjee

The Johns Hopkins University School of Medicine; Baltimore, MD

Sunil Upadhyay

The Johns Hopkins University School of Medicine; Baltimore, MD

Xiaofei Chang

The Johns Hopkins University School of Medicine; Baltimore, MD

Jatin K. Nagpal

The Johns Hopkins University School of Medicine; Baltimore, MD

Barry Trink

The Johns Hopkins University School of Medicine; Baltimore, MD

David Sidransky

The Johns Hopkins University School of Medicine; Baltimore, MD

Purchase article for $19

Subscribe to this journal for $129/year