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Golgi Associated HIF1a Serves as a Reserve in Melanoma Cells.

Authors
  • Lakhter, Alexander J1
  • Lahm, Tim2
  • Broxmeyer, Hal E3
  • Naidu, Samisubbu R1
  • 1 Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, 46202. , (India)
  • 2 Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, 46202. , (India)
  • 3 Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis, Indiana, 46202. , (India)
Type
Published Article
Journal
Journal of Cellular Biochemistry
Publisher
Wiley (John Wiley & Sons)
Publication Date
Apr 01, 2016
Volume
117
Issue
4
Pages
853–859
Identifiers
DOI: 10.1002/jcb.25381
PMID: 26375488
Source
Medline
Keywords
License
Unknown

Abstract

Hypoxia-inducible factor-1alpha (HIF1a) is a key transcriptional regulator that enables cellular metabolic adaptation to low levels of oxygen. Multiple mechanisms, including lysosomal degradation, control the levels of HIF1a protein. Here we show that HIF1a protein degradation is resistant to lysosomal inhibition and that HIF1a is associated with the Golgi compartment in melanoma cells. Although pharmacological inhibitors of prolyl hydroxylation, neddylation and the proteasome inhibited degradation of HIF1a, attenuation of lysosomal activity with chloroquine did not alter the levels of HIF1a or its association with Golgi. Pharmacological disruption of Golgi resulted in nuclear accumulation of HIF1a. However, blockade of ER-Golgi protein transport in hypoxia reduced the transcript levels of HIF1a target genes. These findings suggest a possible role for the oxygen-dependent protein folding process from the ER-Golgi compartment in fine-tuning HIF1a transcriptional output.

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