Parkin targets HIF-1α for ubiquitination and degradation to inhibit breast tumor progression View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-11-28

AUTHORS

Juan Liu, Cen Zhang, Yuhan Zhao, Xuetian Yue, Hao Wu, Shan Huang, James Chen, Kyle Tomsky, Haiyang Xie, Christen A. Khella, Michael L. Gatza, Dajing Xia, Jimin Gao, Eileen White, Bruce G. Haffty, Wenwei Hu, Zhaohui Feng

ABSTRACT

Mutations in E3 ubiquitin ligase Parkin have been linked to familial Parkinson’s disease. Accumulating evidence suggests that Parkin is a tumor suppressor, but the underlying mechanism is poorly understood. Here we show that Parkin is an E3 ubiquitin ligase for hypoxia-inducible factor 1α (HIF-1α). Parkin interacts with HIF-1α and promotes HIF-1α degradation through ubiquitination, which in turn inhibits metastasis of breast cancer cells. Parkin downregulation in breast cancer cells promotes metastasis, which can be inhibited by targeting HIF-1α with RNA interference or the small-molecule inhibitor YC-1. We further identify lysine 477 (K477) of HIF-1α as a major ubiquitination site for Parkin. K477R HIF-1α mutation and specific cancer-associated Parkin mutations largely abolish the functions of Parkin to ubiquitinate HIF-1α and inhibit cancer metastasis. Importantly, Parkin expression is inversely correlated with HIF-1α expression and metastasis in breast cancer. Our results reveal an important mechanism for Parkin in tumor suppression and HIF-1α regulation. More... »

PAGES

1823

References to SciGraph publications

  • 2013-03-17. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization in NATURE
  • 2001-10. Parkin ubiquitinates the α-synuclein–interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease in NATURE MEDICINE
  • 1999-05. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis in NATURE
  • 2006-03. Parkin Modulates Gene Expression in Control and Ceramide-Treated PC12 Cells in MOLECULAR BIOLOGY REPORTS
  • 2009-11-29. Somatic mutations of the Parkinson's disease–associated gene PARK2 in glioblastoma and other human malignancies in NATURE GENETICS
  • 2006-08-21. HIF-1α and EPAS ubiquitination mediated by the VHL tumour suppressor involves flexibility in the ubiquitination mechanism, similar to other RING E3 ligases in ONCOGENE
  • 2008-06-23. Parkin as a tumor suppressor gene for hepatocellular carcinoma in ONCOGENE
  • 2016-01-08. Parkin modulates expression of HIF-1α and HIF-3α during hypoxia in gliobastoma-derived cell lines in vitro in CELL AND TISSUE RESEARCH
  • 2014-06-20. Phosphorylated ubiquitin: a new shade of PINK1 in Parkin activation in CELL RESEARCH
  • 2016-03-30. The ever-expanding role of HIF in tumour and stromal biology in NATURE CELL BIOLOGY
  • 2015-01-23. UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α in NATURE COMMUNICATIONS
  • 2000-07. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase in NATURE GENETICS
  • 2007-11-29. p53 regulates maternal reproduction through LIF in NATURE
  • 2017-04-17. Parkin–phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2013-12-03. An emerging role of PARK2 in cancer in JOURNAL OF MOLECULAR MEDICINE
  • 2012-12-08. Somatic Mutation of PARK2 Tumor Suppressor Gene is not Common in Common Solid Cancers in PATHOLOGY & ONCOLOGY RESEARCH
  • 2012-08-13. Gankyrin promotes breast cancer cell metastasis by regulating Rac1 activity in ONCOGENE
  • 2006-07-23. A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K–Akt signalling in NATURE CELL BIOLOGY
  • 2016-09-08. Structural insights into Parkin substrate lysine targeting from minimal Miro substrates in SCIENTIFIC REPORTS
  • 2015-04-10. Pontin, a new mutant p53-binding protein, promotes gain-of-function of mutant p53 in CELL DEATH & DIFFERENTIATION
  • 2003-11-13. Alterations in the common fragile site gene Parkin in ovarian and other cancers in ONCOGENE
  • 2013-06-17. Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases in NATURE COMMUNICATIONS
  • 2013-06-17. A molecular explanation for the recessive nature of parkin-linked Parkinson’s disease in NATURE COMMUNICATIONS
  • 2012-05-13. MYC suppresses cancer metastasis by direct transcriptional silencing of αv and β3 integrin subunits in NATURE CELL BIOLOGY
  • 2013-12-20. Spliced MDM2 isoforms promote mutant p53 accumulation and gain-of-function in tumorigenesis in NATURE COMMUNICATIONS
  • 2012-07-08. SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors in NATURE
  • 2013-11-07. Tumor metastasis: moving new biological insights into the clinic in NATURE MEDICINE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-017-01947-w

    DOI

    http://dx.doi.org/10.1038/s41467-017-01947-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1092917895

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29180628


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