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Presents
the Friday Keck Center Teleconference*
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Interactions
of the Hepatitis C Virus RNA-dependent RNA Polymerase NS5B with
the Retinoblastoma Tumor Suppressor Protein
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Stanley
Lemon, MD.,
Director,
Institute for Human Infections and Immunity, and Professor,
Internal Medicine-Infectious Diseases and Microbiology, UTMB
Galveston
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4:00
pm Friday
April
20th , 2007
(Refreshments
at 3:45)
5.521
Levin Hall
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Abstract: Chronic
hepatitis C virus (HCV) infection is a major cause of
hepatocellular carcinoma (HCC) worldwide. Hepatic inflammation may
contribute to DNA damage and carcinogenesis, but transgenic mice
expressing HCV proteins have a high rate of HCC even without
inflammation. We have found that HCV regulates expression of the
retinoblastoma tumor suppressor protein (pRb), which plays a
critical role in controlling cellular proliferation and apoptosis
and is targeted by oncoproteins expressed by DNA tumor viruses.
Both total and phospho-pRb abundance are sharply reduced in cells
infected with HCV. Down regulation of pRb is post-transcriptional,
and due to the HCV RNA polymerase, NS5B, which forms a complex
with pRb, targeting it for ubiquitination and proteasome-dependent
degradation. NS5B interacts with pRb through a conserved
Leu-x-Cys/Asn-x-Asp motif, homologous to pRb-binding domains in
DNA virus oncoproteins and overlaping the polymerase active site,
resulting in recruitment of the E3 ubiquitin ligase, E6-associated
protein (E6AP). siRNA knock-down of E6AP rescues pRb abundance in
HCV replicon cells, but E6AP is not capable of NS5B-dependent
ubiquitination of pRb in reconstituted cell-free reactions. This
suggests that additional host or viral proteins are required for
NS5B-dependent ubiquitination of pRb. The down-regulation of pRb
by NS5B results in activation of E2F-responsive promoters and
promotes cellular proliferation. HCV infection may thus stimulate
normally quiescent hepatocytes to proliferate and cause genomic
instability in hepatocytes, thereby setting the stage for liver
cancer.
(
http://www.utmb.edu/ihii/lemon.shtml
)
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The
Keck Friday Seminar*
schedule
for Spring 2007
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12-Jan
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Robert
Cox
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Functional
MRI
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19-Jan
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Ching Lau, Assoc Prof,
Pediatrics, Hematology/Oncology, BCM
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Novel
targets in pediatric brain tumors: from genomics to bedside
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26-Jan
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Irina
I. Serysheva
Baylor
College of Medicine
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Domain
Structure of RyR1 channel at Subnanometer Resolution
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2-Feb
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Poster winners from the
2006 Keck Annual Research Conference
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Matthew
Baker, Kexin Huang, & Jeffrey Reid
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9-Feb
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Mauro Ferrari,
Professor, Brown Foundation Institute of Molecular Medicine for
the Prevention of Human Diseases; Chairman, Dept. of Biomedical
Engineering, UTHSC-H
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Biomedical
Nonotechnology
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16-Feb
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Mike Mancini,
Associate Professor, Dept. of Molecular & Cellular Biology,
BCM
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Single cell
analyses of transcription using high throughput imaging
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23-Feb
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C. Thomas Caskey, Dir.
and COO, Institute for Molecular Medicine, UTHSC-H
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The Drug
Development Crisis: Efficiency and Safety
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2-Mar
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Jack Smith, Dean
& Professor, School of Health Information Sciences, UTHSC-H
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Issues
Related to Open Access and Clinical Data Repositories
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9-Mar
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Midterm
Recess
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16-Mar
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Vittorio Cristini,
Associate Professor, School of Health Information Sciences,
UTHSC-H
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Computational
modeling identifies morphologic predictors of tumor invasion
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23-Mar
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Margaret
Cheung, Assistant Prof, Physics, UH
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Life in a
crowd: macromolecular crowding and confinement effects on protein
interactions in living systems
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30-Mar
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Theodore
S. Jardetzky
Northwestern
University
Professor,
Biochemistry, Molecular Biology & Cell Biology
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Structural
Insights into the Metastable Folding, Refolding and Membrane
Fusion Activity of the Paramyxovirus F Protein.
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6-Apr
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Good
Friday
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13-Apr
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Keith Hodgson, Prof.
Chemistry, Stanford Synchrotron Radiation Laboratory, Stanford
University
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Brighter
than a Quadrillion Suns:
X-ray Free
Electron Lasers and Applications in Structural Dynamics and
Biology
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20-Apr
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Stanley Lemon,
Dir, Institute for Human Infections and Immun; Professor, Internal
Medicine-Infectious Diseases, Microbiology, UTMB
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Interactions
of the hepatitis C virus RNA-dependent RNA polymerase NS5B with
the retinoblastoma tumor suppressor protein
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KECK/HAMP
Friday Seminars: http://xray.utmb.edu/keck
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Archived
Friday Seminar Webcasts Available:
http://cohesion.rice.edu/centersandinst/gcc/
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*Improved
clearer images: Now with POLYCOM's
DUAL STREAMING H.239 technology for clear
high-resolution slides plus video.
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