Novel
Cyclin Functions in Cell Cycle Arrest, Differentiation and Programmed
Cell Death
Comprehensive knowledge of the regulatory proteins in pathways controlling cellular
proliferation, differentiation and migration is essential for understanding the
processes that go awry in neoplastic disease, and provides the basis for the development
of novel therapeutic Our laboratory uses a combination of molecular and cell biological approaches and protein biochemistry
to study the role of cyclin G family members in cellular proliferation and differentiation regulatory
pathways using various model systems. These studies encompass several projects relevant to the fields of
immunology, developmental neuroscience and cancer cell biology (breast, brain, lymphoma and prostate). We
seek to understand the function of these cyclins in specific tumor-suppressor pathways, and the signaling
mechanism(s) and modifications that modulate their expression or activity. Representative
Publications: Click
here to see a list of additional publications Center
and Program affiliations: The
Medical Scientist Training Program Interdisciplinary
Graduate Program in Molecular & Cellular Biology Neuroscience Training Program Free
Radical & Radiation Biology Holden
Comprehensive Cancer Center
Mary
C. Horne, Ph.D.
Assistant Professor
Ph.D. (microbiology)
Ludwig-Maximilians, Germany, 1991
E-mail: mary-horne@uiowa.edu
Office: 2-530 BSB
Phone: (319) 335-8267
interventions. We focus our studies on the novel "G" family (cyclins G1, G2 and I (G3))
of atypical cyclins. Cyclins G1 and G2, in contrast to classical cell cycle promoting cyclins,
are associated with growth inhibitory pathways. They are expressed at relatively low levels in
normal, replicating cells, but upregulated in a variety of cell types during responses to diverse
growth inhibitory stimuli. Both cyclins G1 and G2 are evolutionarily conserved from fish to humans,
suggesting an ancient and important cellular function. We have shown that ectopic expression of cyclins
G1 and G2 leads to a G1/S-phase cell cycle arrest and that cyclin G2, like cyclin G1, associates with
active protein Phosphatase 2A. Recent microarray analyses from a variety of studies have strongly
implicated this unique cyclin family as negative coordinators of the cell cycle and promoters of
cellular differentiation.
We have recently identified several novel cyclin G family interactions. We endeavor to characterize the endogenous
cyclin G1 and G2 protein complexes in native tissues and determine the polypeptide regions required for their
interaction with identified binding partners in order to determine the relevance of these cyclin interactions to
their physiological functions. Specifically, we are interested in the function and mechanisms of action of cyclin G1
and G2 complexes in: 1) Responses to B cell receptor signaling and tolerance induction in developing lymphocytes, 2)
Cell cycle regulation of neurons in the developing cerebellum, 3) Cellular responses to growth-receptor signals, and
genotoxic and environmental stress in breast and prostate cells.