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Myeloid translocation gene-16 co-repressor promotes degradation of hypoxia-inducible factor 1.

Kumar, Parveen LU ; Gullberg, Urban LU ; Olsson, Inge LU and Ajore, Ram LU (2015) In PLoS ONE 10(5).
Abstract
The myeloid translocation gene 16 (MTG16) co-repressor down regulates expression of multiple glycolytic genes, which are targets of the hypoxia-inducible factor 1 (HIF1) heterodimer transcription factor that is composed of oxygen-regulated labile HIF1α and stable HIF1β subunits. For this reason, we investigated whether MTG16 might regulate HIF1 negatively contributing to inhibition of glycolysis and stimulation of mitochondrial respiration. A doxycycline Tet-On system was used to control levels of MTG16 in B-lymphoblastic Raji cells. Results from co-association studies revealed MTG16 to interact with HIF1α. The co-association required intact N-terminal MTG16 residues including Nervy Homology Region 1 (NHR1). Furthermore, electrophoretic... (More)
The myeloid translocation gene 16 (MTG16) co-repressor down regulates expression of multiple glycolytic genes, which are targets of the hypoxia-inducible factor 1 (HIF1) heterodimer transcription factor that is composed of oxygen-regulated labile HIF1α and stable HIF1β subunits. For this reason, we investigated whether MTG16 might regulate HIF1 negatively contributing to inhibition of glycolysis and stimulation of mitochondrial respiration. A doxycycline Tet-On system was used to control levels of MTG16 in B-lymphoblastic Raji cells. Results from co-association studies revealed MTG16 to interact with HIF1α. The co-association required intact N-terminal MTG16 residues including Nervy Homology Region 1 (NHR1). Furthermore, electrophoretic mobility shift assays demonstrated an association of MTG16 with hypoxia response elements (HREs) in PFKFB3, PFKFB4 and PDK1 promoters in-vitro. Results from chromatin immunoprecipitation assays revealed co-occupancy of these and other glycolytic gene promoters by HIF1α, HIF1β and MTG16 in agreement with possible involvement of these proteins in regulation of glycolytic target genes. In addition, MTG16 interacted with prolyl hydroxylase D2 and promoted ubiquitination and proteasomal degradation of HIF1α. Our findings broaden the area of MTG co-repressor functions and reveal MTG16 to be part of a protein complex that controls the levels of HIF1α. (Less)
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published
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in
PLoS ONE
volume
10
issue
5
publisher
Public Library of Science
external identifiers
  • pmid:25974097
  • wos:000354545600007
  • scopus:84929340264
ISSN
1932-6203
DOI
10.1371/journal.pone.0123725
language
English
LU publication?
yes
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6e3c04f6-fa35-412d-a205-fa43931f75d0 (old id 5453213)
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http://www.ncbi.nlm.nih.gov/pubmed/25974097?dopt=Abstract
date added to LUP
2015-06-04 19:56:01
date last changed
2017-04-09 03:46:24
@article{6e3c04f6-fa35-412d-a205-fa43931f75d0,
  abstract     = {The myeloid translocation gene 16 (MTG16) co-repressor down regulates expression of multiple glycolytic genes, which are targets of the hypoxia-inducible factor 1 (HIF1) heterodimer transcription factor that is composed of oxygen-regulated labile HIF1α and stable HIF1β subunits. For this reason, we investigated whether MTG16 might regulate HIF1 negatively contributing to inhibition of glycolysis and stimulation of mitochondrial respiration. A doxycycline Tet-On system was used to control levels of MTG16 in B-lymphoblastic Raji cells. Results from co-association studies revealed MTG16 to interact with HIF1α. The co-association required intact N-terminal MTG16 residues including Nervy Homology Region 1 (NHR1). Furthermore, electrophoretic mobility shift assays demonstrated an association of MTG16 with hypoxia response elements (HREs) in PFKFB3, PFKFB4 and PDK1 promoters in-vitro. Results from chromatin immunoprecipitation assays revealed co-occupancy of these and other glycolytic gene promoters by HIF1α, HIF1β and MTG16 in agreement with possible involvement of these proteins in regulation of glycolytic target genes. In addition, MTG16 interacted with prolyl hydroxylase D2 and promoted ubiquitination and proteasomal degradation of HIF1α. Our findings broaden the area of MTG co-repressor functions and reveal MTG16 to be part of a protein complex that controls the levels of HIF1α.},
  articleno    = {e0123725},
  author       = {Kumar, Parveen and Gullberg, Urban and Olsson, Inge and Ajore, Ram},
  issn         = {1932-6203},
  language     = {eng},
  number       = {5},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Myeloid translocation gene-16 co-repressor promotes degradation of hypoxia-inducible factor 1.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0123725},
  volume       = {10},
  year         = {2015},
}