DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation
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-ubiquit...
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todo:paper_00219258_v287_n36_p30789_Pelisch2023-10-03T14:23:18Z DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation Pelisch, F. Pozzi, B. Risso, G. Muñoz, M.J. Srebrow, A. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219258_v287_n36_p30789_Pelisch |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Pelisch, F. Pozzi, B. Risso, G. Muñoz, M.J. Srebrow, A. DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Pelisch, F. Pozzi, B. Risso, G. Muñoz, M.J. Srebrow, A. |
| author_facet |
Pelisch, F. Pozzi, B. Risso, G. Muñoz, M.J. Srebrow, A. |
| author_sort |
Pelisch, F. |
| title |
DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation |
| title_short |
DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation |
| title_full |
DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation |
| title_fullStr |
DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation |
| title_full_unstemmed |
DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation |
| title_sort |
dna damage-induced heterogeneous nuclear ribonucleoprotein k sumoylation regulates p53 transcriptional activation |
| url |
http://hdl.handle.net/20.500.12110/paper_00219258_v287_n36_p30789_Pelisch |
| work_keys_str_mv |
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| _version_ |
1782024871569522688 |