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Review |
B in Cell Growth Regulation
From the Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia
The nuclear factor (NF)-
B family of eukaryotic transcription
factors plays an important role in the regulation of immune
response, embryo and cell lineage development, cell
apoptosis, cell-cycle progression,
inflammation, and oncogenesis. A wide range of stimuli,
including cytokines, mitogens, environmental
particles, toxic metals, and viral or bacterial
products, activate NF-
B, mostly through I
B kinase
(IKK)-dependent phosphorylation and subsequent degradation of its
inhibitor, the I
B family of proteins. Activated NF-
B
translocates into the nucleus where it modulates the expression of a
variety of genes, including those encoding cytokines,
growth factors, acute phase response proteins, cell
adhesion molecules, other transcription factors, and
several cell apoptosis regulators. During the past few years,
tremendous progress has been achieved in our understanding on how
intracellular signaling pathways are transmitted in either a linear or
a network manner leading to the activation of NF-
B and subsequent
cell growth control. However, a detailed molecular mechanism of
NF-
B regulating cell growth has yet to be determined. Elucidation of
the relationships between NF-
B activation and cell growth will be
important in developing new strategies for the treatment of various
human diseases, such as chronic autoimmune disorder and
cancer.
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