Format

Send to

Choose Destination
BMB Rep. 2016 May;49(5):245-6.

Regulation of HIF-1α stability by lysine methylation.

Author information

1
School of Biological Sciences, Creative Research Initiative Center for Chromatin Dynamics, Seoul National University, Seoul 08826, Korea.
2
Department of Biological Sciences, Sookmyung Women's University, Seoul 04310, Korea.

Abstract

The level and activity of critical regulatory proteins in cells are tightly controlled by several tiers of post-translational modifications. HIF-1α is maintained at low levels under normoxia conditions by the collaboration between PHD proteins and the VHL-containing E3 ubiquitin ligase complex. We recently identified a new physiologically relevant mechanism that regulates HIF-1α stability in the nucleus in response to cellular oxygen levels. This mechanism is based on the collaboration between the SET7/9 methyltransferase and the LSD1 demethylase. SET7/9 adds a methyl group to HIF-1α, which triggers degradation of the protein by the ubiquitin-proteasome system, whereas LSD1 removes the methyl group, leading to stabilization of HIF-1α under hypoxia conditions. In cells from knock-in mice with a mutation preventing HIF-1α methylation (Hif1αKA/KA), HIF-1α levels were increased in both normoxic and hypoxic conditions. Hif1αKA/KA knock-in mice displayed increased hematological parameters, such as red blood cell count and hemoglobin concentration. They also displayed pathological phenotypes; retinal and tumor-associated angiogenesis as well as tumor growth were increased in Hif1αKA/KA knock-in mice. Certain human cancer cells exhibit mutations that cause defects in HIF-1α methylation. In summary, this newly identified methylation-based regulation of HIF-1α stability constitutes another layer of regulation that is independent of previously identified mechanisms. [BMB Reports 2016; 49(5): 245-246].

PMID:
26973343
PMCID:
PMC5070701
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Korean Society for Biochemistry and Molecular Biology Icon for PubMed Central
Loading ...
Support Center