• Skip to primary navigation
  • Skip to main content
SRI InternationalSRI mobile logo

SRI International

SRI International - American Nonprofit Research Institute

  • About
    • Blog
    • Press room
  • Expertise
    • Advanced imaging systems
    • Artificial intelligence
    • Biomedical R&D services
    • Biomedical sciences
    • Computer vision
    • Cyber & formal methods
    • Education and learning
    • Innovation strategy and policy
    • National security
    • Ocean & space
    • Quantum
    • QED-C
    • Robotics, sensors & devices
    • Speech & natural language
    • Video test & measurement
  • Ventures
  • NSIC
  • Careers
  • Contact
  • 日本支社
Show Search
Hide Search
Biomedical sciences publications April 1, 2013 Conference Paper

Development of Functional Assays for p97/VCP Inhibition

SRI International April 1, 2013

SRI Authors: Xiaohe Liu

Citation

Copy to clipboard


Shi, Y., Liu, X., Calaoagan, J., Samuelsson, S., Chou, T.-F., Deshaies, R. J., & Sambucetti, L. C. (2013, 6-10 April). Development of functional assays for p97/VCP inhibition. Paper presented at the Annual Meeting of the American Association for Cancer Research (AACR’13), Washington, DC.

Abstract

p97 (also called VCP in metazoans and CDC48 in yeast) is a highly conserved, ubiquitously expressed, and essential AAA ATPase. p97 plays a key role in endoplasmic reticulum-associated degradation of misfolded secretory and membrane proteins as well as ubiquitin-dependent turnover of a subset of cytoplasmic substrates of the ubiquitin-proteasome system. p97 also plays a critical role in specific cellular processes including Golgi membrane reassembly, membrane fusion, autophagy and DNA repair mechanisms. p97 expression is elevated in a number of cancer types including prostate cancer, non-small-cell lung carcinoma and leukemia. Given its cellular functions in protein homeostasis and the successful clinical development of proteasome inhibitors, p97 has emerged as an exciting new target for cancer therapy. We used p97 siRNA and a recently identified small molecule p97 inhibitor, N2,N4-dibenzylquinazoline- 2,4-diamine (DBeQ) as tools to develop functional assays suitable for further evaluating the activity of potential p97 inhibitors. A panel of unfolded protein response marker genes that are consistently modulated by p97 siRNA or DBeQ treatment has been identified. In addition, methods to monitor autophagic activity have been developed, including high content analysis of LC3B-GFP puncta formation. Cell viability assays were used to determine the susceptibility of various cancer cell lines to p97 inhibition. These assays will be used to evaluate the effects of potential p97 inhibitors on p97-dependent pathways and anti-proliferative activity.

Share this

Facebooktwitterlinkedinmail

Biomedical sciences publications, Publication Conference Paper

How can we help?

Once you hit send…

We’ll match your inquiry to the person who can best help you.

Expect a response within 48 hours.

Career call to action image

Make your own mark.

Search jobs
Our work

Case studies

Publications

Timeline of innovation

Areas of expertise

Blog

Institute

Leadership

Press room

Media inquiries

Compliance

Privacy policy

Careers

Job listings

Contact

SRI Ventures

Our locations

Headquarters

333 Ravenswood Ave
Menlo Park, CA 94025 USA

+1 (650) 859-2000

Subscribe to our newsletter

日本支社

SRI International

  • Contact us
  • Privacy Policy
  • Cookies
  • DMCA
  • Copyright © 2022 SRI International