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Abstract:

Heterogeneous nuclear ribonucleoprotein (hnRNP) K is a nucleocytoplasmic shuttling protein that is a key player in the p53-triggered DNA damage response, acting as a cofactor for p53 in response to DNA damage. hnRNP K is a substrate of the ubiquitin E3 ligase MDM2 and, upon DNA damage, is de-ubiquitylated. In sharp contrast with the role and consequences of the other post-translational modifications, nothing is known about the role of SUMO conjugation to hnRNP K in p53 transcriptional co-activation. In the present work, we show that hnRNP K is modified by SUMO in lysine 422 within its KH3 domain, and sumoylation is regulated by the E3 ligase Pc2/ CBX4. Most interestingly, DNA damage stimulates hnRNP K sumoylation through Pc2 E3 activity, and this modification is required for p53 transcriptional activation. Abrogation of hnRNPKsumoylation leads to an aberrant regulation of the p53 target gene p21. Our findings link the DNA damage-induced Pc2 activation to the p53 transcriptional co-activation through hnRNP K sumoylation. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

Registro:

Documento: Artículo
Título:DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation
Autor:Pelisch, F.; Pozzi, B.; Risso, G.; Muñoz, M.J.; Srebrow, A.
Filiación:Instituto de Fisiología, Biología Molecular Y Neurociencias, Departamento de Fisiología, Biología Molecular Y Celular, Universidad de Buenos Aires, Buenos Aires (C1428EHA), Argentina
Palabras clave:Co-activation; Cofactors; DNA damage response; DNA damages; E3 ligase; Heterogeneous nuclear ribonucleoprotein (hnRNP); Nuclear ribonucleoprotein; Nucleo-cytoplasmic shuttling; Post-translational modifications; Sharp contrast; SUMO conjugation; Sumoylation; Target genes; Transcriptional activations; Ubiquitin; Amino acids; Genes; DNA; DNA; heterogeneous nuclear ribonucleoprotein K; lysine; polycomb group protein; protein p53; SUMO protein; ubiquitin protein ligase E3; article; carboxy terminal sequence; controlled study; DNA damage; enzyme activation; enzyme activity; gene; gene expression regulation; gene targeting; human; human cell; p21 gene; priority journal; protein domain; protein function; signal transduction; sumoylation; transcription initiation; transcription regulation; tumor suppressor gene; ubiquitination; Cell Line, Tumor; DNA Damage; HEK293 Cells; Humans; Polycomb-Group Proteins; Proto-Oncogene Proteins c-mdm2; Ribonucleoproteins; SUMO-1 Protein; Sumoylation; Transcriptional Activation; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases
Año:2012
Volumen:287
Número:36
Página de inicio:30789
Página de fin:30799
DOI: http://dx.doi.org/10.1074/jbc.M112.390120
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:DNA, 9007-49-2; lysine, 56-87-1, 6899-06-5, 70-54-2; CBX4 protein, human, 6.3.2.-; HNRNPK protein, human, 146410-60-8; MDM2 protein, human, 6.3.2.19; Polycomb-Group Proteins; Proto-Oncogene Proteins c-mdm2, 6.3.2.19; Ribonucleoproteins; SUMO-1 Protein; TP53 protein, human; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases, 6.3.2.19
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v287_n36_p30789_Pelisch

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Citas:

---------- APA ----------
Pelisch, F., Pozzi, B., Risso, G., Muñoz, M.J. & Srebrow, A. (2012) . DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation. Journal of Biological Chemistry, 287(36), 30789-30799.
http://dx.doi.org/10.1074/jbc.M112.390120
---------- CHICAGO ----------
Pelisch, F., Pozzi, B., Risso, G., Muñoz, M.J., Srebrow, A. "DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation" . Journal of Biological Chemistry 287, no. 36 (2012) : 30789-30799.
http://dx.doi.org/10.1074/jbc.M112.390120
---------- MLA ----------
Pelisch, F., Pozzi, B., Risso, G., Muñoz, M.J., Srebrow, A. "DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation" . Journal of Biological Chemistry, vol. 287, no. 36, 2012, pp. 30789-30799.
http://dx.doi.org/10.1074/jbc.M112.390120
---------- VANCOUVER ----------
Pelisch, F., Pozzi, B., Risso, G., Muñoz, M.J., Srebrow, A. DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation. J. Biol. Chem. 2012;287(36):30789-30799.
http://dx.doi.org/10.1074/jbc.M112.390120