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Acetylation of SUMO1 Alters Interactions with the SIMs of PML and Daxx in a Protein Specific Manner

55 Pages Posted: 19 Sep 2019 Sneak Peek Status: Published

See all articles by Xavier Mascle

Xavier Mascle

University of Montreal - Department of Biochemistry and Molecular Medicine

Christina Gagnon

University of Montreal - Department of Biochemistry and Molecular Medicine

Haytham M Wahba

University of Montreal - Department of Biochemistry and Molecular Medicine

Mathieu Lussier-Price

University of Montreal - Department of Biochemistry and Molecular Medicine

Laurent Cappadocia

University of Montreal - Department of Biochemistry and Molecular Medicine

Kazuyasu Sakaguchi

Hokkaido University - Department of Chemistry

James Omichinski

University of Montreal - Department of Biochemistry and Molecular Medicine

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Abstract

The interactions between SUMO proteins and SUMO-Interacting Motif (SIM) in nuclear bodies formed by the promyelocytic leukemia (PML) protein (PML-NBs) have been shown to be modulated by either phosphorylation of the SIMs or acetylation of SUMO proteins. However, little is known about how this occurs at the atomic level. In this work, we examined the role that acetylation of SUMO1 plays on its binding to the phosphorylated SIMs (phosphoSIMs) of PML and Daxx. Our results demonstrate that SUMO1 binding to the phosphoSIM of either PML or Daxx is dramatically reduced by acetylation at either K39 or K46. However, acetylation at K37 only impacte binding to PML. Structures of acetylated SUMO1 variants bound to the phosphoSIMs of PML and Daxx demonstrate that there is structural plasticity in SUMO-SIM interactions. The plasticity observed in these structures provides a robust mechanism for regulating SUMO-SIM interactions in PML-NBs using signaling generated post-translational modifications.

Keywords: SUMO, SUMO-intereacting motif, PML, Daxx, acetylation, phosphorylation, PML nuclear bodies, crystallography, ITC, BRET

Suggested Citation

Mascle, Xavier and Gagnon, Christina and Wahba, Haytham M and Lussier-Price, Mathieu and Cappadocia, Laurent and Sakaguchi, Kazuyasu and Omichinski, James, Acetylation of SUMO1 Alters Interactions with the SIMs of PML and Daxx in a Protein Specific Manner (September 19, 2019). Available at SSRN: https://ssrn.com/abstract=3455364 or http://dx.doi.org/10.2139/ssrn.3455364
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Xavier Mascle

University of Montreal - Department of Biochemistry and Molecular Medicine ( email )

2900 Boulevard Edouard-Montpetit
Montréal, Québec H3T 1J4
Canada

Christina Gagnon

University of Montreal - Department of Biochemistry and Molecular Medicine

2900 Boulevard Edouard-Montpetit
Montréal, Québec H3T 1J4
Canada

Haytham M Wahba

University of Montreal - Department of Biochemistry and Molecular Medicine ( email )

2900 Boulevard Edouard-Montpetit
Montréal, Québec H3T 1J4
Canada

Mathieu Lussier-Price

University of Montreal - Department of Biochemistry and Molecular Medicine ( email )

2900 Boulevard Edouard-Montpetit
Montréal, Québec H3T 1J4
Canada

Laurent Cappadocia

University of Montreal - Department of Biochemistry and Molecular Medicine

2900 Boulevard Edouard-Montpetit
Montréal, Québec H3T 1J4
Canada

Kazuyasu Sakaguchi

Hokkaido University - Department of Chemistry ( email )

Sapporo
Japan

James Omichinski (Contact Author)

University of Montreal - Department of Biochemistry and Molecular Medicine ( email )

2900 Boulevard Edouard-Montpetit
Montréal, Québec H3T 1J4
Canada

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