title: DNA damage-induced heterogeneous nuclear ribonucleoprotein K sumoylation regulates p53 transcriptional activation.
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 hnRNP K sumoylation 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.
authors: Instituto de Fisiología, Biología Molecular y Neurociencias-Consejo Nacional de Investigaciones Científicas y Técnicas; Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales-Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, Buenos Aires (C1428EHA), Argentina.
authors: Federico
authors: F
authors: Pelisch
authors: Berta
authors: B
authors: Pozzi
authors: Guillermo
authors: G
authors: Risso
authors: Manuel Javier
authors: MJ
authors: Muñoz
authors: Anabella
authors: A
authors: Srebrow
mesh_terms: D045744:Cell Line, Tumor; D004249:DNA Damage; D057809:HEK293 Cells; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D008025:Ligases; D063146:Polycomb-Group Proteins / Q000096:biosynthesis / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D063146:Polycomb-Group Proteins; D012261:Ribonucleoproteins; D025842:SUMO-1 Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C072074:HNRNPK protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C570427:CBX4 protein, human