SUMO-dependent regulation of centrin-2.
Centrins are multifunctional Ca(2+)-binding proteins that are highly conserved from yeast to humans. Centrin-2 is a core component of the centrosome of higher eukaryotes. In addition, it is present within the nucleus, in which it is part of the xeroderma pigmentosum group C (XPC) complex, which controls nucleotide excision repair (NER). Regulation of the subcellular distribution of centrin-2 has so far remained elusive. Here we show that centrin-2 is a substrate of SUMOylation in vitro and in vivo, and that it is preferentially modified by SUMO2/3. Moreover, we identify the SUMO E3-like ligase human polycomb protein 2 (PC2; also known as hPC2) as essential for centrin-2 modification. Interference with the SUMOylation pathway leads to a striking defect in nuclear localization of centrin-2 and accumulation in the cytoplasm, whereas centrosomal recruitment of centrin-2 is unaffected. Depletion of the XPC protein mimics this situation and we provide evidence that SUMO conjugation of centrin-2 enhances its binding to the XPC protein. These data show that the nucleocytoplasmic shuttling of centrin-2 depends on the SUMO system and indicates that localization of centrin-2 within the nucleus depends on its ability to bind to the XPC protein.
Klein
Ulf R
UR
Department of Cell Biology, Max-Planck Institute of Biochemistry, D-82152 Martinsried, Germany. uklein@biochem.mpg.de
Nigg
Erich A
EA
D000818:Animals; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism / Q000528:radiation effects; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D045706:Proprotein Convertase 2 / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding / Q000528:radiation effects; D011499:Protein Processing, Post-Translational / Q000528:radiation effects; D021381:Protein Transport / Q000528:radiation effects; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014466:Ultraviolet Rays
C472752:CETN2 protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C086984:XPC protein, human; D045706:Proprotein Convertase 2; D046988:Proteasome Endopeptidase Complex