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DNAJB1 negatively regulates MIG6 to promote epidermal growth factor receptor signaling

Authors
 Soo-Yeon Park  ;  Hyo-Kyoung Choi  ;  Jae Sung Seo  ;  Jung-Yoon Yoo  ;  Jae-Wook Jeong  ;  Youngsok Choi  ;  Kyung-Chul Choi  ;  Ho-Geun Yoon 
Citation
 Biochimica et Biophysica Acta - Molecular Cell Research, Vol.1853(10 Pt A) : 2722-2730, 2015 
Journal Title
 Biochimica et Biophysica Acta - Molecular Cell Research 
ISSN
 0167-4889 
Issue Date
2015
Abstract
Mitogen-inducible gene 6 (MIG6) is a tumor suppressor implicated in the development of human cancers; however, the regulatory mechanisms of MIG6 remain unknown. Here, using a yeast two-hybrid screen, we identified DnaJ homolog subfamily B member I (DNAJB1) as a novel MIG6-interacting protein. We found that DNAJB1 binds to and decreases MIG6 protein, but not mRNA, levels. DNAJB1 overexpression dosage-dependently decreased MIG6 protein levels. Conversely, DNAJB1 knockdown increased MIG6 protein levels. DNAJB1 destabilizes MIG6 by enhancing K48-linked ubiquitination of MIG6. However, knocking-down of DNAJB1 reduced the ubiquitination of MIG6. DNAJB1 positively regulates the epidermal growth factor receptors (EGFR) signaling pathway via destabilization of MIG6; however, DNAJB1 knockdown diminishes activation of EGFR signaling as well as elevation of MIG6. Importantly, the increased levels of MIG6 by DNAJB1 knockdown greatly enhanced the gefitinib sensitivity in A549 cells. Thus, our study provides a new molecular mechanism to regulate EGFR signaling through modulation of MIG6 by DNAJB1 as a negative regulator.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140908
DOI
10.1016/j.bbamcr.2015.07.024
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)
Yonsei Authors
박수연(Park, Soo Yeon) ; 서재성(Seo, Jae Sung) ; 유정윤(Yoo, Jung Yoon) ; 윤호근(Yoon, Ho Geun)
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http://www.sciencedirect.com/science/article/pii/S016748891500261X
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