MassIVE MSV000080754

Imported Reanalysis Dataset Public PXD004515

Is transthyretin a regulator of Ubc9 SUMOylation?

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Description

Ageing and mutations of transthyretin (TTR), the thyroid hormones and retinol transporting protein lead to amyloidosis by destabilizing the structure of TTR. Because protein structure is regulated through posttranslational modifications, we investigated the Small Ubiquitin-like Modifier (SUMO)ylation of TTR. We chose the widely used Ubc9 fusion-directed SUMOylation system, which is based on a fusion of the SUMOylation substrate of interest with Ubc9, a sole SUMO conjugating enzyme. Surprisingly, despite our presumptions, we found that Ubc9 fused to TTR was SUMOylated at a unique set of lysine residues. Three unknown SUMOylation sites of Ubc9—K154, K18 and K65—were revealed by mass spectrometry (MS). The previously reported SUMOylation at K49 of Ubc9 was also observed. SUMOylation of the lysine residues of TTR fused to Ubc9 was hardly detectable. However, non-fused TTR was SUMOylated via trans-SUMOylation by Ubc9 fused to TTR. Interestingly, mutating the catalytic residue of Ubc9 fused to TTR did not result in complete loss of the SUMOylation signal, suggesting that Ubc9 linked to TTR is directly cross-SUMOylated by the SUMO-activating enzyme E1. Ubc9, TTR or fusion proteins composed of TTR and Ubc9 specifically affected the global SUMOylation of cellular proteins. TTR or Ubc9 alone increased global SUMOylation, whereas TTR and Ubc9 together decreased the amount of high-molecular weight (HMW) SUMO conjugates. Our data suggest that TTR may influence the SUMOylation of Ubc9, thereby altering signalling pathways in the cell. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: transthyretin ; Ubc9 ; SUMOylation ; UFDS ; post-translational modifications

Contact

Principal Investigators:
(in alphabetical order) 		Sylwia Kedracka-Krok, Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland, N/A
Submitting User: ccms

Publications

Wieczorek E, K?dracka-Krok S, So?tys K, Jankowska U, Ho?ubowicz R, Seliga J, O?yhar A.
Is Transthyretin a Regulator of Ubc9 SUMOylation?.
PLoS ONE. 2016;11(8):e0160536. Epub 2016 Aug 8.

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