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alliedacademies
Archives of Industrial Biotechnology | Volume 2
May 14-15, 2018 | Montreal, Canada
World Yeast Congress
Yeast cells have evolved to maintain steady internal nitrogen
homeostasis in the face of continuous and drastic transitions
in its environmental nitrogen supply. Cells are able to take
full advantage of luxurious nitrogenous environments, while
retaining theability tosuccessfullycopewiththosethat aremore
austere. This Nitrogen Catabolite Repression (NCR) sensitive
control is achieved through the regulation of the GATA-binding
transcription activators, Gln3 and Gat1. In nitrogen replete
conditions Gln3 and Gat1 are efficiently sequestered in the
cytoplasmandasaresult,NCR-sensitivetranscription isminimal.
As nutritional conditions deteriorate, Gln3 and Gat1 relocate to
the nucleus and dramatically increase GATA factor-mediated
transcription of the genes required to import and catabolize
poor nitrogen sources scavenged from the environment. TorC1
kinase complex was originally thought to be the principle
contributor to NCR-sensitive Gln3 regulation. However, Gln3
responds to 5 distinct physiological conditions each exhibiting
a unique set of regulatory requirements. This argued that NCR-
sensitive control was more complex than appreciated. Using
amino acid substitutions throughout the disordered Gln3
protein, we show that nitrogen-responsive TorC1 control only
partially accounts for NCR-sensitive regulation. Uncharged
tRNA-activated, Gcn2 kinase-mediated General Amino Acid
Control (GAAC) isequallycriticalwiththeGcn2andTorC1kinases
functioning independently and in opposition to one another.
Epistasis experiments indicate Gcn2 likely functions upstream
of Ure2, whereas the 14-3-3 proteins Bmh1/2, also required for
nuclear Gln3 localization, likely function downstream. Nuclear
Gln3 import is also more complex than previously appreciated
requiring two additional Nuclear Localization Sequences (NLS)
in addition to the previously reported NLS1 as well as a newly
identified Ure2 Relief Sequence. A third level of Gln3 regulation
is imposed within the nucleus. In high glutamine, Gln3 exits
from the nucleus in the absence of binding to its GATA targets
within NCR-sensitive promoters. In contrast, as glutamine levels
decrease, GATA binding becomes requisite for Gln3 to exit from
the nucleus. It is only through the concerted actions of this
full array of regulatory components that NCR can effectively
manage intra-cellular homeostasis in the face of unreliable
environments.
Speaker Biography
Terrance G Cooper investigated Avian Oil Droplets as an undergraduate and obtained
his MS in Chemistry studying carboxylase enzyme mechanisms at Wayne State and his
PhD at Purdue University. He first discovered that Π-oxidation occurs in peroxisomes
rather than mitochondria with Magasanik at MIT. He investigated the mechanism of
carbon catabolite repression in E. coli. While there he and Patricia Whitney discovered
yeast urea amidolyase to be a multifunctional protein consisting of urea carboxylase
and allophanate hydrolase. Moving to the University of Pittsburgh, he and his students
elucidated the reactions of the allantoin degradative pathway, proposed nitrogen
catabolite repression (NCR) as controlling nitrogen-responsive gene expression and he
authored “The Tools of Biochemistry”. He learned the intricacies of yeast genetics from
Sye Fogel and cloning from John Carbon. His group identified, mapped and cloned and
sequenced the allantoin pathway structural and four GATA-transcriptional regulatory
genes. As Harriet S Van Vleet Professor at the University of Tennessee, he founded
and directed the Molecular Resource Center and was Chair of Microbiology and
Immunology for 15 years. His students identified the promoter structures of the NCR-
sensitive genes, binding sites for their four regulatory transcription factors and now
the regulatory pathways controlling Gln3 localization and intra-nuclear regulation. He
served 17 years on and chaired NIH and ACS study sections, chaired the AAMC Council
of Academic Societies, served on the AAMC Executive Committee, Multiple Editorial
Boards and as Treasure and American Representative to the International Conference
of Yeast Genetics and Molecular Biology. He is currently a member of the UT Board of
Trustees.
e:
Terrance G Cooper
University of Tennessee Health Science Center, USA
The ins and outs of nitrogen-responsive gene regulation in Saccharomyces cerevisiae