Abstract

Although gastrin, CCK and substance P are medically important hormones that have been well studied with regard to structure and physiology, very little is known about the molecular mechansims which regulate their synthesis. The main objective of the proposed research is to further our understading of the molecular events controlling the metabolism and biosynthesis of these hormones by examining the regulation of expression of their genes. The experiments outlined in this proposal include the following areas of investigation: (a) Gastrin, CCK and substance P specific cDNA clones will be isolated and their precursor sequences will be determined. (b) Expression of gastrin, CCK and substance P clones will be attempted in E. coli. (c) Gastrin, CCK and substance P precursor polypeptides will be isolated and used in the study of processing-modification in vivo as well as in vitro. (d) Analogs of gastrin, CCK and substance P precursor will be generated by altering cDNA clones. (e) Isolate and characterize chromosomal genes for gastrin, CCK and substance P. (f) Study the mechanism of initiation of transcription and RNA processing. Since gastrin, CCK and substance P are associated with human diseases, namely gastric carcinoma, obesity and Huntington's and Parkinson's diseases respectively, understanding of the mechanisms which regulate their synthesis may ultimately provide useful new insights into the cause and management of these diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK021901-09
Application #
3227154
Study Section
Endocrinology Study Section (END)
Project Start
1979-05-01
Project End
1988-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Martin, Terence E; Powell, C Thomas; Wang, Zunde et al. (2003) A novel mitogenic protein that is highly expressed in cells of the gastric antrum mucosa. Am J Physiol Gastrointest Liver Physiol 285:G332-43
Yoon, H; Sitikov, A S; Jeon, C et al. (1998) Preferential interaction of the mRNA proofreading factor TFIIS zinc ribbon with rU.dA base pairs correlates with its function. Biochemistry 37:12104-12
Jeon, C; Agarwal, K (1996) Fidelity of RNA polymerase II transcription controlled by elongation factor TFIIS. Proc Natl Acad Sci U S A 93:13677-82
Jeon, C; Yoon, H; Agarwal, K (1994) The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II. Proc Natl Acad Sci U S A 91:9106-10
Montag, A G; Oka, T; Baek, K H et al. (1993) Tumors in hepatobiliary tract and pancreatic islet tissues of transgenic mice harboring gastrin simian virus 40 large tumor antigen fusion gene. Proc Natl Acad Sci U S A 90:6696-700
Ueno, A; Baek, K; Jeon, C et al. (1992) Netropsin specifically enhances RNA polymerase II termination at terminator sites in vitro. Proc Natl Acad Sci U S A 89:3676-80
Yoo, O J; Yoon, H S; Baek, K H et al. (1991) Cloning, expression and characterization of the human transcription elongation factor, TFIIS. Nucleic Acids Res 19:1073-9
Agarwal, K; Baek, K H; Jeon, C J et al. (1991) Stimulation of transcript elongation requires both the zinc finger and RNA polymerase II binding domains of human TFIIS. Biochemistry 30:7842-51