Methylation-dependent regulation of HIF-1α stability restricts retinal and tumour angiogenesis

Yunho Kim, Hye Jin Nam, Junyeop Lee, Do Young Park, Chan Kim, Young Suk Yu, Dongha Kim, Se Won Park, Jinhyuk Bhin, Daehee Hwang, Ho Lee, Gou Young Koh and Sung Hee Baek ()
Additional contact information
Yunho Kim: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University
Hye Jin Nam: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University
Junyeop Lee: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology
Do Young Park: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology
Chan Kim: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology
Young Suk Yu: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University
Dongha Kim: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University
Se Won Park: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University
Jinhyuk Bhin: Institute for Basic Science, DGIST
Daehee Hwang: Institute for Basic Science, DGIST
Ho Lee: Graduate School of Cancer Science and Policy, Research Institute, National Cancer Center
Gou Young Koh: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology
Sung Hee Baek: Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Hypoxia-inducible factor-1α (HIF-1α) mediates hypoxic responses and regulates gene expression involved in angiogenesis, invasion and metabolism. Among the various HIF-1α posttranslational modifications, HIF-1α methylation and its physiological role have not yet been elucidated. Here we show that HIF-1α is methylated by SET7/9 methyltransferase, and that lysine-specific demethylase 1 reverses its methylation. The functional consequence of HIF-1α methylation is the modulation of HIF-1α stability primarily in the nucleus, independent of its proline hydroxylation, during long-term hypoxic and normoxic conditions. Knock-in mice bearing a methylation-defective Hif1aKA/KA allele exhibit enhanced retinal angiogenesis and tumour vascularization via HIF-1α stabilization. Importantly, S28Y and R30Q mutations of HIF-1α, found in human cancers, are involved in the altered HIF-1α stability. Together, these results demonstrate a role for HIF-1α methylation in regulating protein stability, thereby modulating biological output including retinal and tumour angiogenesis, with therapeutic implications in human cancer.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10347 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10347

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10347

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().