Tobacco Documents Online

THE COUNCIL FOR TOBACCO RESEARCH-U.S.A.. INC. 900 111IRD AVENUE NEW YORK. N.Y. 10022 Memorandum To: Dr. H.McAllister and Staff From: D.H.Ford Re: Site visit with Dr.Srilata Bagchi, University of Illinois at Chicago, IL, Nov.3, 1993. Grant No. 3174R2 entitled "Papillomavirus E7 protein and transcription regulation." Aims: Briefly, Dr. Bagchi wants to define the molecular mechanism whereby papilloma virus E7 protein controls the activity of the cellular transcription factor E2F. It appears that the E7 protein can regulate the interaction of the transcription factor E2F with the transcription regulatory protein E2F-BP. Thus, she wants to characterize and purify the components of E2F-BP. Progress: In addition to the publication listed in her progress report, a new one has appeared this past October entitled:Association of the human papilloma type 16 E7 protein with the S-phase-specifici E2F-cyclin A complex. CTR is acknowledged. Details of her progress are adequately discussed in her progress report and need not be repeated here. She is currently pursuing how antioncogenes (p53 and the Rb gene) regulate oncogenes and how oncogenes regulate the transcription of other genes.., in particularly the regulation of the transforming Irowth factor- 1 by adenovirus E1A and papilloma virus E6 and E7 oncogenes. This is a complex issue, but she seems to be making excellent progress. A further issue is, why do sanatic cells sanetimes refuse to respond to TGF- Under so- called normal conditions, there appear to be multiple challenges to both p53 and Rb genes. If then DNA repair fails to correct a 'knock-out' of both of these genes, a malignancy may well occur. Both of these genes are inv6lved with TGF- in that p53 regulates the expression of genes which are promoters for TGF- and Rb regulates TGF- directly. Further, there appear to be a number of gene regulated factors which interfere with the cell cycle at various phases. Ie. the E2F-cyclin A complex which appears only during the S-phase of the cell cycle. Comment: A interesting program, relevent to development of cancer investigating the various inter-related gene-oncogene interactions which influence cell proliferation and differentiation. Dr. Bagchi is a young, enthusiastic investigator who not only understands the intricacies of her area of research, but appears to have a broad understanding of biology as'well. As her studies progress, it seems likely that she will add further knowledge to, our understanding of factors promoting or inhibiting transcriptional regulation of cell proliferation and differentiation. DHF