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DNAJB1 negatively regulates MIG6 to promote epidermal growth factor receptor signaling

Title
 DNAJB1 negatively regulates MIG6 to promote epidermal growth factor receptor signaling
Authors
 Soo-Yeon Park; Hyo-Kyoung Choi; Ho-Geun Yoon; Kyung-Chul Choi; Youngsok Choi; Jae-Wook Jeong; Jung-Yoon Yoo; Jae Sung Seo
Issue Date
2015
Journal Title
 Biochimica et Biophysica Acta - Molecular Cell Research
ISSN
 0167-4889
Citation
 Biochimica et Biophysica Acta - Molecular Cell Research, Vol.1853(10 Pt A) : 2722~2730, 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
http://ir.ymlib.yonsei.ac.kr/handle/22282913/140908
DOI
10.1016/j.bbamcr.2015.07.024
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Biochemistry & Molecular Biology
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S016748891500261X
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