Jab1/CSN5 induces the cytoplasmic localization and degradation of RUNX3.
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.
Kim
Jang-Hyun
JH
Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.
Choi
Joong-Kook
JK
Cinghu
Senthilkumar
S
Jang
Ju-Won
JW
Lee
You-Soub
YS
Li
Ying-Hui
YH
Goh
Yun-Mi
YM
Chi
Xin-Zi
XZ
Lee
Kyeong-Sook
KS
Wee
Heejun
H
Bae
Suk-Chul
SC
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000075686:COP9 Signalosome Complex; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D050677:Core Binding Factor Alpha 3 Subunit / Q000032:analysis* / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D050677:Core Binding Factor Alpha 3 Subunit; D047908:Intracellular Signaling Peptides and Proteins; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex