A novel function of cIAP1 as a mediator of CHIP-driven eIF4E regulation

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473830.do
DOI
10.1038/s41598-017-10358-2
Title
A novel function of cIAP1 as a mediator of CHIP-driven eIF4E regulation
Description
We are grateful to Dr. Lee K.H. at Chosun University for the kind giftof VN173 and VC155 constructs used for the BiFC assays. This researchwas supported by the Basic Science Research Program through the NationalResearch Foundation of Korea (NRF) funded by the Ministry of Education(NRF-2014R1A1A2057451, NRF-2012M3A9C6049933). D.H.J. was supported by aBrain Korea 21 Research Fellowship from the Korean Ministry ofEducation.
abstract
eIF4E is an initiator protein in cap-dependent translation. Its overexpression is linked to tumorigenesis in various human cancers, suggesting that the levels of eIF4E must be under tight control in normal cells. Although several eIF4E regulatory mechanisms have been demonstrated, the intracellular mechanisms controlling eIF4E protein levels remain poorly understood. Here, we report that eIF4E is efficiently regulated by dual mechanisms, both involving human inhibitor of apoptosis family protein cIAP1. cIAP1 itself ubiquitinates eIF4E as an E3 ligase, and interestingly, cIAP1 also functions as a mediator to present eIF4E to another E3 ligase, CHIP. This collaborative activity of cIAP1 and CHIP directs eIF4E toward degradation, controlling its levels and suppressing tumorigenesis. Our results provide the first evidence for a mediator function of cIAP1 and collaborative activity of cIAP1 and CHIP, suggesting that maintaining balanced levels of these E3 ligases might be beneficial for normal cell growth.
provenance
Made available in Cube on 2018-09-28T10:29:58Z (GMT). No. of bitstreams: 0
language
English
author
Seo, Tae Woong
Lee, Ji Sun
Choi, Ye Na
Jeong, Dar Heum
Lee, Sun Kyung
Yoo, Soon Ji
accessioned
2018-09-28T10:29:58Z
available
2018-09-28T10:29:58Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473830.do
Funder
교육부
Funding Program
개인기초연구(교육부)
Project ID
1345270982
Jurisdiction
Rep.of Korea
Project Name
Studies on oncogenic function of Endonuclease G in ovarian cancer and the therapeutic strategy for ovarian cancer
rights
openAccess
type
article


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