|
Research Interests:
Dmp1 (cyclin D binding myb-like protein 1) is a transcription factor isolated in a yeast two-hybrid screen using cyclin D2 as a bait. As a transcription factor, Dmp1 binds to nonameric DNA sequence (CCCGG/TATGT/C) to act as transcriptional activator or repressor. Extensive search of Dmp1 regulated genes revealed that the tumor suppressor role of Dmp1 is mediated through potent activation of Arf, and as a result, stabilization of p53. Dmp1 knockout mice are predisposed to and develop hematologic malignancies and solid tumors after long latency. Activation of oncogenes such as K-Ras and Her2 leads to induction of Dmp1 and subsequent p53-dependent cell cycle arrest. LOH analysis of human lung and breast cancer samples indicates that hDMP1 locus is frequently and specifically disrupted, which is mutually exclusive of p53 inactivation and mutation. Hence, Dmp1 is critical in prevention of early lesions as a result of oncogenic stress.
Based on the amino acid sequence, Dmp1 protein is expected to migrate to ~ 85kDa on a SDS gel. However, Dmp1 is most often observed around 120-130kDa, suggesting extensive post-translational modification. Currently, I am working to identify upstream kinases that can phosphorylate Dmp1. Furthermore, we will map phosphorylation sites and how each one of these modulates Dmp1 transcriptional activity and subcellular localization. Finally, we will attempt to identify physiological conditions that activate kinases upstream of Dmp1 to modulate its activity.
Publications:
Abstracts/Posters:
Dejan Maglic and Timothy J. Bloom., Western blot and RTPCR analysis of phosphodiesterase (PDE4) expression in mouse leg muscle., FASEB J. 22.836.3. 2008.
|