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Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes.

Publication ,  Journal Article
Simões, V; Cizubu, BK; Harley, L; Zhou, Y; Pajak, J; Snyder, NA; Bouvette, J; Borgnia, MJ; Arya, G; Bartesaghi, A; Silva, GM
Published in: Cell Rep
May 24, 2022

Protein ubiquitination is an essential process that rapidly regulates protein synthesis, function, and fate in dynamic environments. Within its non-proteolytic functions, we showed that K63-linked polyubiquitinated conjugates heavily accumulate in yeast cells exposed to oxidative stress, stalling ribosomes at elongation. K63-ubiquitinated conjugates accumulate mostly because of redox inhibition of the deubiquitinating enzyme Ubp2; however, the role and regulation of ubiquitin-conjugating enzymes (E2) in this pathway remained unclear. Here, we show that the E2 Rad6 associates and modifies ribosomes during stress. We further demonstrate that Rad6 and its human homolog UBE2A are redox regulated by forming a reversible disulfide with the E1 ubiquitin-activating enzyme (Uba1). This redox regulation is part of a negative feedback regulation, which controls the levels of K63 ubiquitination under stress. Finally, we show that Rad6 activity is necessary to regulate translation, antioxidant defense, and adaptation to stress, thus providing an additional physiological role for this multifunctional enzyme.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

May 24, 2022

Volume

39

Issue

8

Start / End Page

110860

Location

United States

Related Subject Headings

  • Ubiquitination
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Activating Enzymes
  • Ribosomes
  • Oxidative Stress
  • Oxidation-Reduction
  • Humans
  • 31 Biological sciences
  • 1116 Medical Physiology
  • 0601 Biochemistry and Cell Biology
 

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Simões, V., Cizubu, B. K., Harley, L., Zhou, Y., Pajak, J., Snyder, N. A., … Silva, G. M. (2022). Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes. Cell Rep, 39(8), 110860. https://doi.org/10.1016/j.celrep.2022.110860
Simões, Vanessa, Blanche K. Cizubu, Lana Harley, Ye Zhou, Joshua Pajak, Nathan A. Snyder, Jonathan Bouvette, et al. “Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes.Cell Rep 39, no. 8 (May 24, 2022): 110860. https://doi.org/10.1016/j.celrep.2022.110860.
Simões V, Cizubu BK, Harley L, Zhou Y, Pajak J, Snyder NA, et al. Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes. Cell Rep. 2022 May 24;39(8):110860.
Simões, Vanessa, et al. “Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes.Cell Rep, vol. 39, no. 8, May 2022, p. 110860. Pubmed, doi:10.1016/j.celrep.2022.110860.
Simões V, Cizubu BK, Harley L, Zhou Y, Pajak J, Snyder NA, Bouvette J, Borgnia MJ, Arya G, Bartesaghi A, Silva GM. Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes. Cell Rep. 2022 May 24;39(8):110860.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

May 24, 2022

Volume

39

Issue

8

Start / End Page

110860

Location

United States

Related Subject Headings

  • Ubiquitination
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Activating Enzymes
  • Ribosomes
  • Oxidative Stress
  • Oxidation-Reduction
  • Humans
  • 31 Biological sciences
  • 1116 Medical Physiology
  • 0601 Biochemistry and Cell Biology