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VDUP1 mediates nuclear export of HIF1alpha via CRM1-dependent pathway

Cited 40 time in Web of Science Cited 46 time in Scopus
Authors
Shin, Daesung; Jeon, Jun-Ho; Jeong, Mira; Suh, Hyun-Woo; Kim, Seyl; Kim, Hyoung-Chin; Moon, Og-Sung; Kim, Yong-Sung; Chung, Jin Woong; Yoon, Suk Ran; Kim, Woo-Ho; Choi, Inpyo
Issue Date
2007-11-07
Publisher
Elsevier
Citation
Biochim. Biophys. Acta 1783 (2008) 838-848
Keywords
HIF1αpVHLVDUP1CRM1Transport
Abstract
Hypoxia-inducible factor 1alpha (HIF1alpha) is a critical transcriptional factor for inducing tumor metastasis, and stabilized under hypoxia but degraded by von Hippel-Lindau protein (pVHL) under normoxia. For the maximal degradation of HIF1alpha, it must be exported to the cytoplasm via an unidentified transporter. Here, we demonstrate that vitamin D3 up-regulated protein 1 (VDUP1) associates with the beta-domain of pVHL and enhances the interaction between pVHL and HIF1alpha to promote the nuclear export and degradation of HIF1alpha hypoxia-independently. Blocking of VDUP1 translocation either by leptomycin B or by nuclear export signal mutation inhibited the nuclear export of pVHL/HIF1alpha and relieved the destabilization of HIF1alpha. VDUP1 suppressed cell invasiveness and tumor metastasis, which were also recovered by blocking of nuclear export. Taken together, these findings indicate that VDUP1 is a novel tumor suppressor which mediates the nuclear export of pVHL/HIF1alpha complex to destabilize HIF1alpha.
ISSN
0006-3002
Language
English
URI
http://hdl.handle.net/10371/3701
DOI
https://doi.org/10.1016/j.bbamcr.2007.10.012

https://doi.org/10.1016/j.bbamcr.2007.10.012
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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