Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation

J. Zhang; F. Zhu; X. Li; Z. Dong; Y. Xu; C. Peng; S. Li; Y. Y. Cho; K. Yao; T. A. Zykova; A. M. Bode; Z. Dong

doi:10.1038/onc.2011.369

Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation

J. Zhang
, F. Zhu
, X. Li
, Z. Dong
, Y. Xu
, C. Peng
, S. Li
, Y. Y. Cho
, K. Yao
, T. A. Zykova
, A. M. Bode
, Z. Dong

University of Minnesota Twin Cities
Zhengzhou University

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

The c-Jun transcription factor is a highly unstable oncoprotein. Several ubiquitin ligases mediate c-Jun degradation. However, c-Jun can be stabilized once it is phosphorylated at the N-terminus by c-Jun N-terminal kinases (JNKs) or other protein kinases. This phosphorylation decreases c-Jun ubiquitination and degradation. The underlying mechanism for this phenomenon is still unknown. Here, we show that receptor for activated C-kinase 1 (Rack1) can bind with c-Jun and ubiquitin ligase Fbw7 to form a complex. When c-Jun is phosphorylated at the N-terminus, c-Jun is released from the complex and cannot be ubiquitinated by Fbw7, which leads to increased stabilization and accumulation of c-Jun. These results reveal that Rack1 has a very important role in tumorigenesis by maintaining the stability of c-Jun that has been phosphorylated at its N-terminus by JNKs or other kinases.

Original language	English
Pages (from-to)	1835-1844
Number of pages	10
Journal	Oncogene
Volume	31
Issue number	14
DOIs	https://doi.org/10.1038/onc.2011.369
State	Published - 5 Apr 2012

Bibliographical note

Funding Information:
We thank Dr Wang Luhai and Dr Ronai Ze’ev for providing the HA-FL-Rack1, HA-WD1-4-Rack1 and HA-WD5-7-Rack1 vectors and Dr Wei Wenyi for providing the Flag-wtc-Jun, Flag-DJNK-c-Jun, Flag-AF-c-Jun and Flag-AF-DJNK-c-Jun plasmids. We also thank Dr Bohmann Dirk for providing the c-JunAlaand c-JunAspmutant c-Jun plasmids. This study was supported by The Hormel Foundation and National Institutes of Health grants CA077646, CA111536, CA120388, ES016548 and R37 CA081064.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Rack1
c-Jun
cell transformation
degradation
phosphorylation

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10.1038/onc.2011.369

Cite this

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title = "Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation",

abstract = "The c-Jun transcription factor is a highly unstable oncoprotein. Several ubiquitin ligases mediate c-Jun degradation. However, c-Jun can be stabilized once it is phosphorylated at the N-terminus by c-Jun N-terminal kinases (JNKs) or other protein kinases. This phosphorylation decreases c-Jun ubiquitination and degradation. The underlying mechanism for this phenomenon is still unknown. Here, we show that receptor for activated C-kinase 1 (Rack1) can bind with c-Jun and ubiquitin ligase Fbw7 to form a complex. When c-Jun is phosphorylated at the N-terminus, c-Jun is released from the complex and cannot be ubiquitinated by Fbw7, which leads to increased stabilization and accumulation of c-Jun. These results reveal that Rack1 has a very important role in tumorigenesis by maintaining the stability of c-Jun that has been phosphorylated at its N-terminus by JNKs or other kinases.",

keywords = "Rack1, c-Jun, cell transformation, degradation, phosphorylation",

author = "J. Zhang and F. Zhu and X. Li and Z. Dong and Y. Xu and C. Peng and S. Li and Cho, \{Y. Y.\} and K. Yao and Zykova, \{T. A.\} and Bode, \{A. M.\} and Z. Dong",

note = "Funding Information: We thank Dr Wang Luhai and Dr Ronai Ze{\textquoteright}ev for providing the HA-FL-Rack1, HA-WD1-4-Rack1 and HA-WD5-7-Rack1 vectors and Dr Wei Wenyi for providing the Flag-wtc-Jun, Flag-DJNK-c-Jun, Flag-AF-c-Jun and Flag-AF-DJNK-c-Jun plasmids. We also thank Dr Bohmann Dirk for providing the c-JunAlaand c-JunAspmutant c-Jun plasmids. This study was supported by The Hormel Foundation and National Institutes of Health grants CA077646, CA111536, CA120388, ES016548 and R37 CA081064.",

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doi = "10.1038/onc.2011.369",

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T1 - Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation

AU - Zhang, J.

AU - Zhu, F.

AU - Li, X.

AU - Dong, Z.

AU - Xu, Y.

AU - Peng, C.

AU - Li, S.

AU - Cho, Y. Y.

AU - Yao, K.

AU - Zykova, T. A.

AU - Bode, A. M.

AU - Dong, Z.

N1 - Funding Information: We thank Dr Wang Luhai and Dr Ronai Ze’ev for providing the HA-FL-Rack1, HA-WD1-4-Rack1 and HA-WD5-7-Rack1 vectors and Dr Wei Wenyi for providing the Flag-wtc-Jun, Flag-DJNK-c-Jun, Flag-AF-c-Jun and Flag-AF-DJNK-c-Jun plasmids. We also thank Dr Bohmann Dirk for providing the c-JunAlaand c-JunAspmutant c-Jun plasmids. This study was supported by The Hormel Foundation and National Institutes of Health grants CA077646, CA111536, CA120388, ES016548 and R37 CA081064.

PY - 2012/4/5

Y1 - 2012/4/5

N2 - The c-Jun transcription factor is a highly unstable oncoprotein. Several ubiquitin ligases mediate c-Jun degradation. However, c-Jun can be stabilized once it is phosphorylated at the N-terminus by c-Jun N-terminal kinases (JNKs) or other protein kinases. This phosphorylation decreases c-Jun ubiquitination and degradation. The underlying mechanism for this phenomenon is still unknown. Here, we show that receptor for activated C-kinase 1 (Rack1) can bind with c-Jun and ubiquitin ligase Fbw7 to form a complex. When c-Jun is phosphorylated at the N-terminus, c-Jun is released from the complex and cannot be ubiquitinated by Fbw7, which leads to increased stabilization and accumulation of c-Jun. These results reveal that Rack1 has a very important role in tumorigenesis by maintaining the stability of c-Jun that has been phosphorylated at its N-terminus by JNKs or other kinases.

AB - The c-Jun transcription factor is a highly unstable oncoprotein. Several ubiquitin ligases mediate c-Jun degradation. However, c-Jun can be stabilized once it is phosphorylated at the N-terminus by c-Jun N-terminal kinases (JNKs) or other protein kinases. This phosphorylation decreases c-Jun ubiquitination and degradation. The underlying mechanism for this phenomenon is still unknown. Here, we show that receptor for activated C-kinase 1 (Rack1) can bind with c-Jun and ubiquitin ligase Fbw7 to form a complex. When c-Jun is phosphorylated at the N-terminus, c-Jun is released from the complex and cannot be ubiquitinated by Fbw7, which leads to increased stabilization and accumulation of c-Jun. These results reveal that Rack1 has a very important role in tumorigenesis by maintaining the stability of c-Jun that has been phosphorylated at its N-terminus by JNKs or other kinases.

KW - Rack1

KW - c-Jun

KW - cell transformation

KW - degradation

KW - phosphorylation

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SN - 0950-9232

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JO - Oncogene

JF - Oncogene

IS - 14

ER -

Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation

Abstract

Bibliographical note

UN SDGs

Keywords

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