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Ubiquitin Modification by the E3 Ligase/ADP-Ribosyltransferase Dtx3L/Parp9.
Yang, Chun-Song; Jividen, Kasey; Spencer, Adam; Dworak, Natalia; Ni, Li; Oostdyk, Luke T; Chatterjee, Mandovi; Kusmider, Beata; Reon, Brian; Parlak, Mahmut; Gorbunova, Vera; Abbas, Tarek; Jeffery, Erin; Sherman, Nicholas E; Paschal, Bryce M.
Afiliación
  • Yang CS; Center for Cell Signaling, University of Virginia, West Complex, 1335 Lee Street, Charlottesville, VA 22908, USA.
  • Jividen K; Center for Cell Signaling, University of Virginia, West Complex, 1335 Lee Street, Charlottesville, VA 22908, USA.
  • Spencer A; Center for Cell Signaling, University of Virginia, West Complex, 1335 Lee Street, Charlottesville, VA 22908, USA.
  • Dworak N; Center for Cell Signaling, University of Virginia, West Complex, 1335 Lee Street, Charlottesville, VA 22908, USA.
  • Ni L; Center for Cell Signaling, University of Virginia, West Complex, 1335 Lee Street, Charlottesville, VA 22908, USA.
  • Oostdyk LT; Center for Cell Signaling, University of Virginia, West Complex, 1335 Lee Street, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia, PO Box 800733, Charlottesville, VA 22908, USA.
  • Chatterjee M; Center for Cell Signaling, University of Virginia, West Complex, 1335 Lee Street, Charlottesville, VA 22908, USA.
  • Kusmider B; Center for Cell Signaling, University of Virginia, West Complex, 1335 Lee Street, Charlottesville, VA 22908, USA.
  • Reon B; Department of Biochemistry and Molecular Genetics, University of Virginia, PO Box 800733, Charlottesville, VA 22908, USA.
  • Parlak M; Department of Radiation Oncology, University of Virginia, PO Box 800383, Charlottesville, VA 22908, USA.
  • Gorbunova V; Department of Biology, University of Rochester, 434 Hutchison Hall, Rochester, NY 14627, USA.
  • Abbas T; Center for Cell Signaling, University of Virginia, West Complex, 1335 Lee Street, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia, PO Box 800733, Charlottesville, VA 22908, USA; Department of Radiation Oncology, University of Virginia, PO Box
  • Jeffery E; W. M. Keck Biomedical Mass Spectrometry Laboratory, University of Virginia, Pinn Hall, Room 1034, Charlottesville, VA 22908, USA.
  • Sherman NE; W. M. Keck Biomedical Mass Spectrometry Laboratory, University of Virginia, Pinn Hall, Room 1034, Charlottesville, VA 22908, USA.
  • Paschal BM; Center for Cell Signaling, University of Virginia, West Complex, 1335 Lee Street, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia, PO Box 800733, Charlottesville, VA 22908, USA. Electronic address: paschal@virginia.edu.
Mol Cell ; 66(4): 503-516.e5, 2017 May 18.
Article en En | MEDLINE | ID: mdl-28525742
ABSTRACT
ADP-ribosylation of proteins is emerging as an important regulatory mechanism. Depending on the family member, ADP-ribosyltransferases either conjugate a single ADP-ribose to a target or generate ADP-ribose chains. Here we characterize Parp9, a mono-ADP-ribosyltransferase reported to be enzymatically inactive. Parp9 undergoes heterodimerization with Dtx3L, a histone E3 ligase involved in DNA damage repair. We show that the Dtx3L/Parp9 heterodimer mediates NAD+-dependent mono-ADP-ribosylation of ubiquitin, exclusively in the context of ubiquitin processing by E1 and E2 enzymes. Dtx3L/Parp9 ADP-ribosylates the carboxyl group of Ub Gly76. Because Gly76 is normally used for Ub conjugation to substrates, ADP-ribosylation of the Ub carboxyl terminus precludes ubiquitylation. Parp9 ADP-ribosylation activity therefore restrains the E3 function of Dtx3L. Mutation of the NAD+ binding site in Parp9 increases the DNA repair activity of the heterodimer. Moreover, poly(ADP-ribose) binding to the Parp9 macrodomains increases E3 activity. Dtx3L heterodimerization with Parp9 enables NAD+ and poly(ADP-ribose) regulation of E3 activity.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Adenosina Difosfato Ribosa / Poli(ADP-Ribosa) Polimerasas / Ubiquitina / Ubiquitina-Proteína Ligasas / Proteínas de Neoplasias / Neoplasias Límite: Humans Idioma: En Año: 2017 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Adenosina Difosfato Ribosa / Poli(ADP-Ribosa) Polimerasas / Ubiquitina / Ubiquitina-Proteína Ligasas / Proteínas de Neoplasias / Neoplasias Límite: Humans Idioma: En Año: 2017 Tipo del documento: Article