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Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation.
Scott, Daniel C; Rhee, David Y; Duda, David M; Kelsall, Ian R; Olszewski, Jennifer L; Paulo, Joao A; de Jong, Annemieke; Ovaa, Huib; Alpi, Arno F; Harper, J Wade; Schulman, Brenda A.
Afiliação
  • Scott DC; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Rhee DY; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Duda DM; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Kelsall IR; MRC Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK.
  • Olszewski JL; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Paulo JA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • de Jong A; Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
  • Ovaa H; Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Department of Chemical Immunology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Alpi AF; MRC Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK.
  • Harper JW; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: wade_harper@hms.harvard.edu.
  • Schulman BA; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: brenda.schulman@stjude.org.
Cell ; 166(5): 1198-1214.e24, 2016 Aug 25.
Article em En | MEDLINE | ID: mdl-27565346
ABSTRACT
Hundreds of human cullin-RING E3 ligases (CRLs) modify thousands of proteins with ubiquitin (UB) to achieve vast regulation. Current dogma posits that CRLs first catalyze UB transfer from an E2 to their client substrates and subsequent polyubiquitylation from various linkage-specific E2s. We report an alternative E3-E3 tagging cascade many cellular NEDD8-modified CRLs associate with a mechanistically distinct thioester-forming RBR-type E3, ARIH1, and rely on ARIH1 to directly add the first UB and, in some cases, multiple additional individual monoubiquitin modifications onto CRL client substrates. Our data define ARIH1 as a component of the human CRL system, demonstrate that ARIH1 can efficiently and specifically mediate monoubiquitylation of several CRL substrates, and establish principles for how two distinctive E3s can reciprocally control each other for simultaneous and joint regulation of substrate ubiquitylation. These studies have broad implications for CRL-dependent proteostasis and mechanisms of E3-mediated UB ligation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ubiquitinas / Proteínas de Transporte / Ubiquitina / Ubiquitina-Proteína Ligases / Ubiquitinação Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ubiquitinas / Proteínas de Transporte / Ubiquitina / Ubiquitina-Proteína Ligases / Ubiquitinação Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2016 Tipo de documento: Article