Regulation of Protein Metabolism in Mammalian Cells: Role oftRNA
{'Code': '08070400', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Kamal Shukla', 'PO_EMAI': None, 'PO_PHON': None}
Most cells respond to amino acid deprivation with a number of                   compensatory or adaptive biochemical changes including slower                   synthesis of protein and RNA, stimulated protein breakdown and                  growth arrest.  In bacteria this "stringent response" is mediated               by ppGpp, a regulatory nucleotide formed when deacylated tRNA                   binds to idle ribosomes.  Mammalian cells respond to amino acid                 deprivation with analogous metabolic changes but ppGpp has not                  been found and the regulatory role of tRNA has been questioned.                 Work from this laboratory has provided clear evidence that in the               stimulation of protein degradation by histidine starvation in CHO               cells, the regulatory mechanism does recognize the level of his-                tRNA and ribosomes idling in the histidine codon.  Therefore, a                 mechanism does exist in mammalian cells comparable to the                       bacterial stringent response, except for the absence of ppGpp.                  This research will:  (i) inquire into the nature of the signal                  emerging from idle ribosomes and attempt to reproduce some of the               regulatory events in cell-free systems; and  (ii) explore the                   physiological significance of this tRNA-dependent response in                   growth control, protection from mistranslation, and maintenance                 of amino acid pools.                                                                                                                                            Unicellular organisms are exposed to changes in the environment                 in which they live.  They compensate for the scarcity of some                   substances by increased transport or biosynthesis and adjust                    their growth rate to the availability of nutrients.  In higher                  organisms, tissue specialization and hormonal regulation maintain               relatively constant concentrations of nutrients in the body                     fluids.  Mammalian cells are capable, however, of a direct                      response to amino acid deprivation which includes slower                        synthesis of RNA and protein, faster protein breakdown, and                     arrest of growth.  The response is analogous to that in bacteria                where the physiological changes following deprivation of a                      required amino acid are collectively known as the "stringent                    response".  The bacterial stringent response is the result of a                 regulatory mechanism sensitive to the level of amino acylation of               tRNAs.  Evidence from this laboratory supports the existence of a               comparable mechanism in cultured cells.
{'FirstName': 'Oscar', 'LastName': 'Scornik', 'PI_MID_INIT': 'A', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Oscar A Scornik', 'EmailAddress': None, 'PI_PHON': None, 'NSF_ID': '000106774', 'StartDate': '07/15/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Dartmouth College', 'CityName': 'HANOVER', 'ZipCode': '037552170', 'PhoneNumber': '6036463007', 'StreetAddress': '7 LEBANON ST', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'New Hampshire', 'StateCode': 'NH', 'CONGRESSDISTRICT': '02', 'CONGRESS_DISTRICT_ORG': 'NH02', 'ORG_UEI_NUM': 'EB8ASJBCFER9', 'ORG_LGL_BUS_NAME': 'TRUSTEES OF DARTMOUTH COLLEGE', 'ORG_PRNT_UEI_NUM': 'EB8ASJBCFER9'}
{'Name': None, 'CityName': None, 'StateCode': None, 'ZipCode': None, 'StreetAddress': None, 'CountryCode': None, 'CountryName': None, 'StateName': None, 'CountryFlag': None, 'CONGRESSDISTRICT': None, 'CONGRESS_DISTRICT_PERF': '""'}
{'Code': '1144', 'Text': 'Molecular Biophysics'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8803517.xml'}