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 language | English (US) |
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Pages (from-to) | 4009-4017 |
Number of pages | 9 |
Journal | Journal of Biological Chemistry |
Volume | 289 |
Issue number | 7 |
DOIs | |
State | Published - Feb 14 2014 |
Externally published | Yes |