The CUL7/F-box and WD repeat domain containing 8 (CUL7/ Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1

Huamin Wang, Yue Chen, Ping Lin, Lei Li, Guisheng Zhou, Guangchao Liu, Craig Logsdon, Jianping Jin, James L. Abbruzzese, Tse Hua Tan

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Background: HPK1 is lost in 95% pancreatic cancer through proteasome-mediated degradation. Results: The ubiquitination and degradation of HPK1 mediated by CUL7/Fbxw8 ubiquitin ligase required HPK1 kinase activity and autophosphorylation. Conclusion: Targeted HPK1 degradation by CUL7/Fbxw8 ubiquitin ligase constitutes a negative-feedback loop to restrain HPK1 activity. Significance: Our study revealed a direct link of CUL7/Fbxw8 ubiquitin ligase to the MAPK pathway.

Original languageEnglish (US)
Pages (from-to)4009-4017
Number of pages9
JournalJournal of Biological Chemistry
Volume289
Issue number7
DOIs
StatePublished - Feb 14 2014

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