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SUMO regulates p21Cip1 intracellular distribution and with p21Cip1 facilitates multiprotein complex formation in the nucleolus upon DNA damage

Abstract: We previously showed that p21Cip1 transits through the nucleolus on its way from the nucleus to the cytoplasm and that DNA damage inhibits this transit and induces the formation of p21Cip1-containing intranucleolar bodies (INoBs). Here, we demonstrate that these INoBs also contain SUMO-1 and UBC9, the E2 SUMO-conjugating enzyme. Furthermore, whereas wild type SUMO-1 localized in INoBs, a SUMO-1 mutant, which is unable to conjugate with proteins, does not, suggesting the presence of SUMOylated proteins at INoBs. Moreover, depletion of the SUMO-conjugating enzyme UBC9 or the sumo hydrolase SENP2 changed p21Cip1 intracellular distribution. In addition to SUMO-1 and p21Cip1, cell cycle regulators and DNA damage checkpoint proteins, including Cdk2, Cyclin E, PCNA, p53 and Mdm2, and PML were also detected in INoBs. Importantly, depletion of UBC9 or p21Cip1 impacted INoB biogenesis and the nucleolar accumulation of the cell cycle regulators and DNA damage checkpoint proteins following DNA damage. The impact of p21Cip1 and SUMO-1 on the accumulation of proteins in INoBs extends also to CRM1, a nuclear exportin that is also important for protein translocation from the cytoplasm to the nucleolus. Thus, SUMO and p21Cip1 regulate the transit of proteins through the nucleolus, and that disruption of nucleolar export by DNA damage induces SUMO and p21Cip1 to act as hub proteins to form a multiprotein complex in the nucleolus.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: PLoS One. 2017 Jun 5;12(6):e0178925

Editorial: Public Library of Science

 Fecha de publicación: 01/06/2017

Nº de páginas: 21

Tipo de publicación: Artículo de Revista

 DOI: 10.1371/journal.pone.0178925

ISSN: 1932-6203

Autores/as

BRUN, SONIA

ABELLA, NEUS

MARIA TERESA BERCIANO BLANCO

OLGA TAPIA MARTINEZ

JAUMOT, MONTSERRAT

FREIRE, RAIMUNDO

MIGUEL ANGEL LAFARGA COSCOJUELA

AGELL, NEUS