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

doi:10.1074/jbc.M113.520106

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 journal › Article › peer-review

41 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 language	English (US)
Pages (from-to)	4009-4017
Number of pages	9
Journal	Journal of Biological Chemistry
Volume	289
Issue number	7
DOIs	https://doi.org/10.1074/jbc.M113.520106
State	Published - Feb 14 2014
Externally published	Yes

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

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.",

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

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T1 - The CUL7/F-box and WD repeat domain containing 8 (CUL7/ Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1

AU - Wang, Huamin

AU - Chen, Yue

AU - Lin, Ping

AU - Li, Lei

AU - Zhou, Guisheng

AU - Liu, Guangchao

AU - Logsdon, Craig

AU - Jin, Jianping

AU - Abbruzzese, James L.

AU - Tan, Tse Hua

PY - 2014/2/14

Y1 - 2014/2/14

N2 - 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.

AB - 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.

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

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