UC San Diego

The ubiquitously expressed nonreceptor tyrosine kinase ABL becomes activated and accumulates in the nucleus when cells undergo DNA damage. Nuclear ABL can then stimulate apoptosis when the cell is unable to repair its DNA. Here we have discovered novel mechanisms in which nuclear ABL regulates cellular DNA damage response. We have identified that ABL can significantly enhance the production of the pro-apoptosis protein PUMA in a post-transcriptional manner. We have also found that nuclear ABL is necessary for p21 activation following DNA damage in the absence of p53. We further expanded our studies into microRNAs, and have found that ABL can phosphorylate the Microprocessor protein DGCR8 in order to stimulate selective microRNA processing of pro-apoptotic microRNAs. Together, our results provide new insights on the role of ABL in DNA damage response