Protein-protein interaction plays a major role in all biological processes. In our lab, we are interested in understanding how extracellular signals are translated into molecular events that change cellular fates. We focus on the stress activated protein kinase (SAPK) known as the c-Jun N-terminal kinase (JNK) as a signaling pathway paradigm and the AP-1 transcription factor as a transcription factor affected by this SAPK/JNK pathway.
Currently the lab focuses on the characterization of two proteins that were originally isolated by the Aronheim’s lab JDP2 and WDR62.
JDP2 was originally isolated based on its ability to associate with c-Jun. JDP2 is an ubiquitously expressed basic leucine zipper (bZIP) protein. JDP2 is an AP-1 transcription repressor protein. The JDP2 closest homologue protein is the Activating Transcription Factor 3 (ATF3). ATF3 is an immediate early transcription factor which plays a major role in stress response and cellular homeostasis. The role of the bZIP repressors in cardiac hypertrophy and heart remodeling is currently under investigation. In addition, the dual role of JDP2 and ATF3 in carcinogenesis is studied. The study focuses in mice with either gain of function or loss of function mutations for the JDP2 and ATF3 proteins.
WDR62 is a novel JNK scaffold protein which was isolated based on its ability to associate with JNK. WDR62 displays no sequence homology with any known protein in the databank. Interestingly, WDR62 was found to be mutated in patients with microcephaly. We focus our study to biochemically characterize WDR62 structure and function and interested to explore WDR62 cellular function in health and in disease state.