DNA Damage-induced hnRNP K SUMOylation Regulates p53 Transcriptional Activation

POZZI, BERTA; PELISCH FEDERICO; RISSO, GUILLERMO; SREBROW ANABELLA

Mendoza

Congreso; Reunion Anual de la Sociedad Argentina de Investigacion en Bioquimica y Biología Molecular; 2012

SAIB

Heterogeneous nuclear ribonucleoprotein (hnRNP) K is a nucleocytoplasmic shuttling protein that regulates mRNA metabolism and is a key player in the p53-triggered DNA damage response. hnRNP K acts as a cofactor for p53 upon DNA damage. In this context, hnRNP K and p53 levels are stabilized upon inhibition of their E3 ubiquitin ligase MDM2, and together they induce the transcription of genes involved in cell cycle arrest. In the present work, we show that hnRNP K is conjugated to SUMO in its lysine 422, within its KH3 domain. This modification is stimulated upon DNA damage and is required for the induction of p53 target genes such as p21 and 14-3-3 s. We further show that hnRNP K sumoylation is regulated by the SUMO E3 ligase Pc2: over- expression of an activity-deficient mutant Pc2 abrogates hnRNP K- triggered p53-dependent transcription. Our findings link the DNA damage-induced Pc2 activation to the p53 transcriptional co-activation through hnRNP K sumoylation.