Jab1/CSN5 induces the cytoplasmic localization and degradation of RUNX3 | Zendy

Kim JangHyun | Zendy; Choi JoongKook | Zendy; Cinghu Senthilkumar | Zendy; Jang JuWon | Zendy; Lee YouSoub | Zendy; Li YingHui | Zendy; Goh YunMi | Zendy; Chi XinZi | Zendy; Lee KyeongSook | Zendy; Wee Heejun | Zendy; Bae SukChul | Zendy

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Jab1/CSN5 induces the cytoplasmic localization and degradation of RUNX3

Author(s) -

Kim JangHyun,

Choi JoongKook,

Cinghu Senthilkumar,

Jang JuWon,

Lee YouSoub,

Li YingHui,

Goh YunMi,

Chi XinZi,

Lee KyeongSook,

Wee Heejun,

Bae SukChul

Publication year - 2009

Publication title -

journal of cellular biochemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.028

H-Index - 165

eISSN - 1097-4644

pISSN - 0730-2312

DOI - 10.1002/jcb.22157

Subject(s) - nuclear export signal , cop9 signalosome , microbiology and biotechnology , proteasome , biology , skp1 , cytoplasm , ubiquitin , nuclear localization sequence , transcription factor , nuclear protein , protein degradation , suppressor , kinase , cancer research , cancer , ubiquitin ligase , cell nucleus , gene , genetics , biochemistry , enzyme , protease , peptide hydrolases

Runt‐related (RUNX) transcription factors play pivotal roles in neoplastic development and have tissue‐specific developmental roles in hematopoiesis ( RUNX1 ), osteogenesis ( RUNX2 ), as well as neurogenesis and thymopoiesis ( RUNX3 ). RUNX3 is a tumor suppressor in gastric carcinoma, and its expression is frequently inactivated by DNA methylation or its protein mislocalized in many cancer types, including gastric and breast cancer. Jun‐activation domain‐binding protein 1 (Jab1/CSN5), a component of the COP9 signalosome (CSN), is critical for nuclear export and the degradation of several tumor suppressor proteins, including p53, p27 Kip1 , and Smad4. Here, we find that Jab1 facilitates nuclear export of RUNX3 that is controlled by CSN‐associated kinases. RUNX3 sequestered in the cytoplasm is rapidly degraded through a proteasome‐mediated pathway. Our results identify a novel mechanism of regulating nuclear export and protein stability of RUNX3 by the CSN complex. J. Cell. Biochem. 107: 557–565, 2009. © 2009 Wiley‐Liss, Inc.

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