A Mouse Model Uncovers LKB1 as an UVB-Induced DNA Damage Sensor Mediating CDKN1A (p21WAF1/CIP1) Degradation

What is it about?

The mechanisms of UV-induced DNA damage response still remain elusive. CDKN1A/p21 (cip1) plays a fundamental role in DNA damage response such as checkpoint-mediated cell cycle arrest, transcription, apoptosis, and DNA repair. Previous findings have suggested a participation of p21 in DNA repair, suggesting that p21 degradation is necessary for optimal DNA repair, although this aspect has remained for long time controversial. In this puzzle, which is the missing link between UV-induced ATR activation and p21 degradation? Here we uncover the new role of LKB1 as a DNA damage sensor protein regulating skin UV-induced DNA damage response, which LKB1 together its downstream kinase NUAK1 bind and phosphorylate CDKN1A/p21(cip1), resulting in the proteosomal degradation of CDKN1A/p21(cip1) and DNA repair.

Featured Image

Why is it important?

This discovery elucidate (1) the missing pieces in the DNA damage response puzzle, identifying LKB1 as the missing link between ATR and the physiological regulation of CDKN1A in response to UVB; (2) the new role of the tumor suppressor serine/threonine kinase LKB1 as an UVB induced DNA damage sensor and (3) the LKB1 mutational status as a potential prognostic risk factor for UV-induced skin cancer.