TY - JOUR
T1 - Protection from Isopeptidase-Mediated Deconjugation Regulates Paralog-Selective Sumoylation of RanGAP1
AU - Zhu, Shanshan
AU - Goeres, Jacqueline
AU - Sixt, Katherine M.
AU - Békés, Miklós
AU - Zhang, Xiang Dong
AU - Salvesen, Guy S.
AU - Matunis, Michael J.
N1 - Funding Information:
We thank members of the Matunis laboratory and Drs. Judith Bender and Val Culotta for insightful discussions during the course of this work. We are grateful to Joshua Sims and Yuan Lin for assistance with Biacore-related experiments and data analysis and Dr. Mary Dasso for providing SENP1 antibodies. This work was supported by a grant from the National Institutes of Health (GM060980 to M.J.M.).
PY - 2009/3/13
Y1 - 2009/3/13
N2 - Vertebrates express three small ubiquitin-related modifiers (SUMO-1, SUMO-2, and SUMO-3) that are conjugated in part to unique subsets of proteins and, thereby, regulate distinct cellular processes. Mechanisms regulating paralog-selective sumoylation, however, remain poorly understood. Despite being equally well modified by SUMO-1 and SUMO-2 in vitro, RanGAP1 is selectively modified by SUMO-1 in vivo. We have found that this paralog-selective modification is determined at the level of deconjugation by isopeptidases. Our findings indicate that, relative to SUMO-2-modified RanGAP1, SUMO-1-modified RanGAP1 forms a more stable, higher affinity complex with the nucleoporin Nup358/RanBP2 that preferentially protects it from isopeptidases. By swapping residues in SUMO-1 and SUMO-2 responsible for Nup358/RanBP2 binding, or by manipulating isopeptidase expression levels, paralog-selective modification of RanGAP1 could be affected both in vitro and in vivo. Thus, protection from isopeptidases, through interactions with SUMO-binding proteins, represents an important mechanism defining paralog-selective sumoylation.
AB - Vertebrates express three small ubiquitin-related modifiers (SUMO-1, SUMO-2, and SUMO-3) that are conjugated in part to unique subsets of proteins and, thereby, regulate distinct cellular processes. Mechanisms regulating paralog-selective sumoylation, however, remain poorly understood. Despite being equally well modified by SUMO-1 and SUMO-2 in vitro, RanGAP1 is selectively modified by SUMO-1 in vivo. We have found that this paralog-selective modification is determined at the level of deconjugation by isopeptidases. Our findings indicate that, relative to SUMO-2-modified RanGAP1, SUMO-1-modified RanGAP1 forms a more stable, higher affinity complex with the nucleoporin Nup358/RanBP2 that preferentially protects it from isopeptidases. By swapping residues in SUMO-1 and SUMO-2 responsible for Nup358/RanBP2 binding, or by manipulating isopeptidase expression levels, paralog-selective modification of RanGAP1 could be affected both in vitro and in vivo. Thus, protection from isopeptidases, through interactions with SUMO-binding proteins, represents an important mechanism defining paralog-selective sumoylation.
KW - PROTEINS
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U2 - 10.1016/j.molcel.2009.02.008
DO - 10.1016/j.molcel.2009.02.008
M3 - Article
C2 - 19285941
AN - SCOPUS:61649103141
SN - 1097-2765
VL - 33
SP - 570
EP - 580
JO - Molecular cell
JF - Molecular cell
IS - 5
ER -