Type

Journal Article

Authors

Cormac T. Taylor
Gerard Cagney
Eoin P. Cummins
Ambrose Clarke
Ulrike Bruning
Carsten C. Scholz
Katrina M Comerford
Alex Cheong
Terence A Agbor

Subjects

Biochemistry

Topics
cysteine endopeptidases senp2 protein human humans physiology hela cells sumo 1 protein glycolysis cell hypoxia protein processing post translational genetics adenosine triphosphate metabolism small ubiquitin related modifier proteins sumo2 protein human

Small ubiquitin-related modifier (SUMO)-1 promotes glycolysis in hypoxia. (2010)

Abstract Under conditions of hypoxia, most eukaryotic cells undergo a shift in metabolic strategy, which involves increased flux through the glycolytic pathway. Although this is critical for bioenergetic homeostasis, the underlying mechanisms have remained incompletely understood. Here, we report that the induction of hypoxia-induced glycolysis is retained in cells when gene transcription or protein synthesis are inhibited suggesting the involvement of additional post-translational mechanisms. Post-translational protein modification by the small ubiquitin related modifier-1 (SUMO-1) is induced in hypoxia and mass spectrometric analysis using yeast cells expressing tap-tagged Smt3 (the yeast homolog of mammalian SUMO) revealed hypoxia-dependent modification of a number of key glycolytic enzymes. Overexpression of SUMO-1 in mammalian cancer cells resulted in increased hypoxia-induced glycolysis and resistance to hypoxia-dependent ATP depletion. Supporting this, non-transformed cells also demonstrated increased glucose uptake upon SUMO-1 overexpression. Conversely, cells overexpressing the de-SUMOylating enzyme SENP-2 failed to demonstrate hypoxia-induced glycolysis. SUMO-1 overexpressing cells demonstrated focal clustering of glycolytic enzymes in response to hypoxia leading us to hypothesize a role for SUMOylation in promoting spatial re-organization of the glycolytic pathway. In summary, we hypothesize that SUMO modification of key metabolic enzymes plays an important role in shifting cellular metabolic strategies toward increased flux through the glycolytic pathway during periods of hypoxic stress.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Cormac T. Taylor, Gerard Cagney, Eoin P. Cummins, Ambrose Clarke, Ulrike Bruning, Carsten C. Scholz, Katrina M Comerford, Alex Cheong, Terence A Agbor

Experts in our system

1
Cormac T. Taylor
University College Dublin
Total Publications: 110
 
2
Gerard Cagney
Royal College of Surgeons in Ireland
Total Publications: 54
 
3
Eoin P. Cummins
University College Dublin
Total Publications: 53
 
4
Ulrike Bruning
University College Dublin
Total Publications: 10
 
5
Carsten C Scholz
University College Dublin
Total Publications: 21
 
6
Alex Cheong
University College Dublin
Total Publications: 18