DNA damage-induced hnRNP K SUMOylation regulates p53 transcriptional activation

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

Saxtons River

Conferencia; FASEB Conference on Ubiquitin & Cellular Regulation; 2012

FASEB

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 co-factor for p53 in response to DNA damage and is a substrate of the ubiquitin E3 ligase MDM2. Upon DNA damage, hnRNP K is de-ubiquitylated and consequently binds to p53-responsive promoters. In sharp contrast with the role and consequences of ubiquitylation and other post-translational modifications, nothing is known about the role of SUMO conjugation to hnRNP K. In the present work, we show that hnRNP K is modified by SUMO in lysine 422 within its KH3 domain. Transfection assays demonstrate that neither ubiquitin nor NEDD8 are conjugated to Lys 422. hnRNP K 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. Our findings link the DNA-damage induced Pc2 activation to the p53 transcriptional co-activation through hnRNP K sumoylation.