Gene Regulation

Dr. David L. Levens, Head, Gene Regulation Section
Building 10, Room 2S235C
(301) 496-2176

To learn more, visit Dr. Leven's CCR Web site.

General Information

Mailing Address:
Gene Regulation Section 
Laboratory of Pathology, CCR
National Cancer Institute
9000 Rockville Pike
Building 10, Room 2N106
Bethesda, MD 20892

Contact Information

The Gene Regulation Section, Laboratory of Pathology, CCR, NCI studies the regulation of the transcription of the human c-myc proto-oncogene. The disregulation of this gene is implicated in the pathogenesis of a variety of human neoplasms. As a key regulator of cell growth and apoptosis, even minor perturbation of c-myc levels disturb the timing and progression of cell growth, the cell cycle, and proliferation. Despite intense and prolonged effort in many groups, the rules governing c-myc regulation have not been fully exposed. No model system including transient expression, stable transfection (either genomic or episomal) or transgenic animals has succeeded in conferring proper physiological regulation upon an exogenously introduced c-myc. Therefore either principle components or processes are missing or defective in these model systems. In addition to conventional transcription factors, the c-myc promoter binds multiple sequence specific and conformation sensitive DNA binding proteins, several of these were discovered and characterized in our group (FBPs 1-3, FIR, and hnRNPK ). The focus of the section since discovering these factors has been to elucidate the roles of these unusual proteins in the regulation of c-myc, FBP activation and FIR repression have been shown to operate through TFIIH and to delay or hasten promoter escape by paused RNA polymerase. Operation of the FBP-FIR-TFIIH system is defective in Xeroderma pigmentosum B and D, bearing mutated TFIIH subunits. Ongoing studies will relate this system to the physiological and biochemical processes and events that demand participation by these sequence and conformation sensitive nucleic acid binding proteins and to define the physiological and biochemical constraints demanding their participation.

Research Topics