Timothy P. Bender
Primary AppointmentMicrobiology, Immunology, and Cancer Biology
- BA, Biology, Albion College, Albion, MI
- MS, Epidemiology, The University of Michigan, Ann Arbor, MI
- PhD, Microbiology and Immunology, The University of Michigan, Ann Arbor, MI
Regulation of gene expression during lymphocyte development
Given the importance of appropriately regulated c-myb expression, our laboratory has been interested in determining the mechanisms that regulate c-myb expression and activity. We have demonstrated the primary mechanism that regulates expression of c-myb mRNA is a conditional block to transcription elongation (attenuation) that occurs in the first intron of the c-myb locus. We are particularly interested characterizing signaling pathways that impact on the efficiency of this block to transcription elongation during lymphocyte development and induction of effector function. As potential targets of c-myb activity have been identified it has become apparent that c-myb is involved in the regulation of lineage and stage specific genes as well as genes that are expressed in most cell types. Thus, identifying mechanisms that regulate c-myb activity poses an interesting problem. We have identified and characterized a major site of phosphorylation on c-myb. Significantly, this site is located in a region of the c-myb protein that is deleted in transforming forms of c-myb and serves to differentially regulate c-myb on some target promoters but not others. We will examine the potential role of this phosphorylation site in activating c-myb transforming potential as well as in regulating c-myb activity during hematopoiesis. Phosphorylation does not modulate the ability of c-myb to bind DNA and we postulate that it likely regulates interaction between c-myb and other proteins that serve to modulate c-myb activity. We have identified several candidate interaction partners and are in the process of characterizing them.