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P TItE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. SUPPORTING BIOMEDICAL INVESTIGATION Mem or andum To: Dr. H. McAllister and Staff Fran: D.H. Ford 900 THIRD AvENuE NEW YORK. NY 10022 (212) 421-8885 Re: Site visit with Dr. K. Calame, Columbua University, P & S, Nov. 9, 1994. Site visitors: D.H.Ford and G. Hashim. Grant No. 3970 entitled "Association of onccprotein c-Myc with transcription regulator YYI." Progress: Inasmuch as CTR support for this program was only initiated -t'is past July, progress beyond where her investigations were in July has been limited, partially since she also carries a teaching and administrative load. However, it was clear from our discussion that the program has been progressing and that is worth CTR support. The primary goal of this program appears to be to determine how the c-Myc onccprotein functions in determining how or when cells will proliferate, differentiate or undergo apo tosis. In part, the c-Myc protein appears to exert its role in cel].response in association with its re lati onship with the transripti ona l regu lat or protein Yin-Y ang-1 (YY-1) . This zinc finger protein possesses different functional properties depending on which protein it associates with. Thus, it can activate, repress or initiate transcripticn. Thus, Dr. Calame's specific aims are: 1.To determine which regions of YYL and c-Myc are required for their association. 2. To determine the ability of YY1/c-Myc complexes to bind to DNA containing the appropriate binding sites. 3.Determine the effect of c-Myc on the initi at or activity of YY1. 4. Determine the ef fe ct of YY 1 on the transcription activity of c-Myc. and 5. Determine the biologic importance of the YY1-c-Myc association. It would appear from the overview of the problem which Dr. Calame presented it that there are various mechanisms whereby c-Myc can alter cell grawth, possibly by altering the expression of YYi dependent genes. This is a complex project and Dr. Calame appears to have the ability to undertake it. Further, if she is successful in achieving her various aims, the information obtained should prove useful in improving our understanding of the multiple f.actors involved in in pr om oting or preventing deve 1 opment of a malignant os 1l line. DHF