Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription

Dachun Yao, Tetsuya Taguchi, Takeshi Matsumura, Richard Pestell, Diane Edelstein, Ida Giardino, Guntram Suske, Naila Ahmed, Paul J. Thornalley, Vijay P. Sarthy, Hans Peter Hammes, Michael Brownlee

Research output: Contribution to journalArticle

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Abstract

Methylglyoxal is a highly reactive dicarbonyl degradation product formed from triose phosphates during glycolysis. Methylglyoxal forms stable adducts primarily with arginine residues of intracellular proteins. The biologic role of this covalent modification in regulating cell function is not known. Here, we report that in retinal Müller cells, increased glycolytic flux causes increased methylglyoxal modification of the corepressor mSin3A. Methylglyoxal modification of mSin3A results in increased recruitment of O-GlcNAc transferase to an mSin3A-Sp3 complex, with consequent increased modification of Sp3 by O-linked N-acetylglucosamine. This modification of Sp3 causes decreased binding of the repressor complex to a glucose-responsive GC box in the angiopoietin-2 promoter, resulting in increased Ang-2 expression. A similar mechanism involving methylglyoxal-modification of other coregulator proteins may play a role in the pathobiology of a variety of conditions associated with changes in methylglyoxal concentration, including cancer and diabetic vascular disease.

Original languageEnglish (US)
Pages (from-to)275-286
Number of pages12
JournalCell
Volume124
Issue number2
DOIs
StatePublished - Jan 27 2006

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Angiopoietin-2
Pyruvaldehyde
Glycolysis
Transcription
Trioses
Diabetic Angiopathies
Co-Repressor Proteins
Acetylglucosamine
Arginine
Proteins
Phosphates
Fluxes
Glucose
Degradation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Yao, D., Taguchi, T., Matsumura, T., Pestell, R., Edelstein, D., Giardino, I., ... Brownlee, M. (2006). Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription. Cell, 124(2), 275-286. https://doi.org/10.1016/j.cell.2005.11.024

Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription. / Yao, Dachun; Taguchi, Tetsuya; Matsumura, Takeshi; Pestell, Richard; Edelstein, Diane; Giardino, Ida; Suske, Guntram; Ahmed, Naila; Thornalley, Paul J.; Sarthy, Vijay P.; Hammes, Hans Peter; Brownlee, Michael.

In: Cell, Vol. 124, No. 2, 27.01.2006, p. 275-286.

Research output: Contribution to journalArticle

Yao, D, Taguchi, T, Matsumura, T, Pestell, R, Edelstein, D, Giardino, I, Suske, G, Ahmed, N, Thornalley, PJ, Sarthy, VP, Hammes, HP & Brownlee, M 2006, 'Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription', Cell, vol. 124, no. 2, pp. 275-286. https://doi.org/10.1016/j.cell.2005.11.024
Yao D, Taguchi T, Matsumura T, Pestell R, Edelstein D, Giardino I et al. Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription. Cell. 2006 Jan 27;124(2):275-286. https://doi.org/10.1016/j.cell.2005.11.024
Yao, Dachun ; Taguchi, Tetsuya ; Matsumura, Takeshi ; Pestell, Richard ; Edelstein, Diane ; Giardino, Ida ; Suske, Guntram ; Ahmed, Naila ; Thornalley, Paul J. ; Sarthy, Vijay P. ; Hammes, Hans Peter ; Brownlee, Michael. / Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription. In: Cell. 2006 ; Vol. 124, No. 2. pp. 275-286.
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