SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

T U M O R C E L L B I O L O G Y P R O G R A M
• MUC4 in the mammary gland is regulated at
the post-transcriptional level by extracellular
matrix (basement membrane) and by TGF-β.
Responses to both of these are known to change
during breast cancer progression.
• MUC4 regulation in the uterus during pregnancy
is at the transcript level, indicating the
complexity of the control of its gene.
• MUC4 overexpression increases primary tumor
growth in nude mice, acting as an antiapoptotic
agent in the growing tumors and in
cell culture.
• MUC4 regulates the localization of the receptor
tyrosine kinase ErbB2 in polarized epithelial
cells.
MURRAY P. DEUTSCHER, PH.D.
Professor and Chairman of Biochemistry
and Molecular Biology
DESCRIPTION OF RESEARCH
Researchers in Dr. Deutscher’s laboratory
focus on two major areas of research. One
deals with the identification, characterization,
and determination of the physiological role of
RNA processing and degradative enzymes. To
date, eight exoribonucleases and seven endo-ribonucleases
have been identified in Escheichia coli.
Many of the enzymes have been purified and
studied for their catalytic properties. Mutations
have been constructed in the genes for each of
these enzymes, and the genes have been cloned
and their sequences identified. Several of these
enzymes have now been shown to participate in
transfer RNA and ribosomal RNA maturation,
and in messenger RNA degradation. The availability
of the purified enzymes and of mutants
lacking these RNases is being used to elucidate
complete RNA maturation pathways and to
study the regulation of these processes. In addition,
his studies have shown that cells contain
RNA quality control mechanisms for eliminating
defective RNA molecules.
The second area of investigation deals with
the translation system of mammalian cells. Protein
synthesis in mammalian cells proceeds as
much as 100-fold faster than synthesis in isolated
cell-free systems. What is lost in these in vitro
systems is the organization that normally exists in
vivo. They have shown that many of the components
of the translation apparatus are associated
with each other, and that protein synthesis is a
“channeled” pathway, i.e., the aminoacyl-tRNA
and peptidyl-tRNA intermediates are directly
transferred from one component of the translation
apparatus to the next without dissociation
into the cellular fluid. A permeabilized mammalian
cell system has been developed that allows
study of these events in close to an in vivo situation.
Studies are in progress to determine the role
of the actin cytoskeleton in maintaining the organization
of the translation system and to identify
other factors associated with the translation apparatus
that affect its function. Dr. Deutscher’s
laboratory has taken this work further to show
that the whole mammalian cell is highly organized
and that macromolecules don’t diffuse, but move
in motor-driven processes on the cytoskeleton.
SELECTED PUBLICATIONS
2002
Li, Z and Deutscher, MP . RNase E plays an essential
role in the maturation of Escherichia coli
tRNA precursors. RNA 8:97-109, 2002.
Li, Z, Reimers, S, Pandit, S, and Deutscher, MP .
RNA quality control: degradation of defective
transfer RNA. EMBO Journal 21:1132-38, 2002.
Cheng, ZF and Deutscher, MP . Purification and
characterization of the Escherichia coli
exoribonuclease RNase R. Comparison with
RNase II. Journal of Biological Chemistry
277:21624-29, 2002.
Zuo, Y and Deutscher, MP . The physiological
role of RNase T can be explained by its unusual
substrate specificity. Journal of Biological Chemistry
277:29654-61, 2002.
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 71