RRC ID 30917
Author Gur I, Fujiwara K, Hasegawa K, Yoshikawa K.
Title Necdin promotes ubiquitin-dependent degradation of PIAS1 SUMO E3 ligase.
Journal PLoS One
Abstract Necdin, a pleiotropic protein that promotes differentiation and survival of mammalian neurons, is a member of MAGE (melanoma antigen) family proteins that share a highly conserved MAGE homology domain. Several MAGE proteins interact with ubiquitin E3 ligases and modulate their activities. However, it remains unknown whether MAGE family proteins interact with SUMO (small ubiquitin-like modifier) E3 ligases such as PIAS (protein inhibitor of activated STAT) family, Nsmce2/Mms21 and Cbx4/Pc2. In the present study, we examined whether necdin interacts with these SUMO E3 ligases. Co-immunoprecipitation analysis revealed that necdin, MAGED1, MAGEF1 and MAGEL2 bound to PIAS1 but not to Nsmce2 or Cbx4. These SUMO E3 ligases bound to MAGEA1 but failed to interact with necdin-like 2/MAGEG1. Necdin bound to PIAS1 central domains that are highly conserved among PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates STAT1 and PML (promyelocytic leukemia protein). Remarkably, necdin promoted degradation of PIAS1 via the ubiquitin-proteasome pathway. In transfected HEK293A cells, amino- and carboxyl-terminally truncated mutants of PIAS1 bound to necdin but failed to undergo necdin-dependent ubiquitination. Both PIAS1 and necdin were associated with the nuclear matrix, where the PIAS1 terminal deletion mutants failed to localize, implying that the nuclear matrix is indispensable for necdin-dependent ubiquitination of PIAS1. Our data suggest that necdin suppresses PIAS1 both by inhibiting SUMO E3 ligase activity and by promoting ubiquitin-dependent degradation.
Volume 9(6)
Pages e99503
Published 2014-1-1
DOI 10.1371/journal.pone.0099503
PII PONE-D-14-06529
Description HEK293T細胞でのSTAT1及びPMLのSumoylation assayに使用されました。
PMID 24911587
PMC PMC4049815
MeSH Animals Cell Line Humans Melanoma-Specific Antigens / metabolism Mice Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Nuclear Proteins / genetics Nuclear Proteins / metabolism* Proteasome Endopeptidase Complex / metabolism Protein Binding Protein Inhibitors of Activated STAT / chemistry Protein Inhibitors of Activated STAT / metabolism* Protein Interaction Domains and Motifs Proteolysis Substrate Specificity Sumoylation Ubiquitin / metabolism* Ubiquitin-Protein Ligases / metabolism* Ubiquitination
IF 2.74
Times Cited 8
DNA material pRSFlag_mmSumo1 (RDB06126)