Mary Horne, Ph.D.
Research/Academic Interests
Unconventional cyclin function during cellular growth, differentiation and stress responses
Synopsis: Insight into the cell cycle regulatory proteins that restrict cellular proliferation and
promote differentiation is essential for understanding the processes that go awry in neoplastic and
developmental diseases. Improved knowledge of these proteins and their mechanisms will further
the development of novel therapeutic interventions for these diseases. We are investigating the
contributions of the novel "G" family of unconventional cyclins to growth control, with a current
emphasis on cyclin G2. Contrasting the prototypical CDK-activating cyclins that are upregulated in
proliferating cells and promote cell cycle progression, elevated expression of cyclins G1 and G2
correlates with growth arrest and induces cell cycle arrest in transfected cells. Importantly, the gene
encoding cyclin G1 is directly activated by the transcription factor and tumor suppressor p53,
whereas the gene encoding cyclin G2 is directly regulated by the stress activated forkhead box O
transcription factors FOXO1 and FOXO3a linked to tumor expression. As both cyclins G1 and G2
are evolutionarily conserved from fish to humans, and knock-out of the single cyclin G homolog in
Drosophila is embryonic lethal, members of this unique cyclin family likely serve important
functions in regulatory pathways that modulate growth and development.
We and others found that cyclin G2 levels are significantly upregulated in cells responding to
diverse cell cycle-inhibitory signals (e.g. blockade of growth factor signaling, induction of oxidative
and genotoxic stress, cellular differentiation), but downregulated upon induction of pro-growth
mitogenic signals (e.g. estrogen, insulin, Shh, IL-4, LPS). Our work showed that ectopically
expressed cyclin G2 inhibits CDK2 activity and induces a G1/S-phase cell cycle arrest that requires
intact p53. We determined that cyclin G2 is a PP2A and centrosome-associated nucleocytoplasmic
shuttling protein that may modulate microtubule stability and regrowth. Emerging studies suggest
that repression of cyclin G2 expression promotes cellular growth and replication. Current research
projects in the laboratory are focused on defining the regulation and function of cyclin G2 during:
1) cellular responses to therapeutics-induced inhibition of endocrine and growth factor signaling
pathways in breast cancers and B cell lymphomas, 2) cellular responses to genotoxic stress and
DNA damaging cancer therapeutics, and 3) the differentiation and post-mitotic growth of neurons.
Graduate Group Affiliations:
Biochemistry, Molecular, Cellular and Development Biology
Title
Specialty
Assistant Professor Adjunct
Pharmacology
Mary Horne, Ph.D.
Department
Address/Phone
Pharmacology
Genome and Biomedical Sciences Building, Genome & Biomedical Sciences Facility, 451 Health
Sciences Drive Suite 3503 Davis, CA 95616
Phone: 530-752-3200
Additional Phone
Phone: 530-752-7723
Email
mhorne@ucdavis.edu
Education
Ph.D., Ludwig-Maximillians University, Muchich Germany
Ph.D., Max- Planck Institution for Biochemistry
M.A., San Francisco State University, San Francisco CA
B.S., California Polytechnic State University, San Luis Obispo, CA
Select Recent Publications
Bennin D.A., Arachchige Don, A.S., Brake T., McKenzie, J.L., Rosenbaum H., Ortiz L., DePaoliRoach A. and Horne, M.C.: Cyclin G2 Associates with Protein Phosphatase 2A Catalytic and
Regulatory B' Subunits in Active Complexes and Induces Nuclear Aberrations and a G1/S Phase
Cell Cycle Arrest. J. Biol. Chem. 277:27449-27467, 2002.
Zhao, L., Samuels, T., Winckler, S., Korgaonkar, C., Tompkins, V., Horne, M.C., Quelle, D.E.:
Cyclin G1 has growth inhibitory activity that is linked to ARF, Mdm2, and p53 function. Molecular
Cancer Research 1:195-206, 2003.
Arachchige Don, A.S., Dallapiazza, R., Bennin, D. A., Brake, T., Cowan, C., and Horne, M.C.:
Cyclin G2 is a centrosome associated nucleo-cytoplasmic shuttling protein that influences
microtubule stability and induces a p53-dependent cell cycle arrest. Exp Cell Res 312:4181-4204,
2006.
Le, X-F., Arachchige-Don, A.S. , Mao, W., *Horne, M.C. and *Bast, Jr., R. C. Roles of HER2, JNK,
PI3K, and p70S6K Pathways in Regulation of Cyclin G2 Expression in Human Breast Cancer Cells.
Mol Can Ther 6(11):2843-2857, 2007. *Senior authorship shared equally.
Mary Horne, Ph.D.
Zhou, J., Su, P., Wang, L., Chen, J., Zimmermann, M., Genbacev, O., Afonja, O., Horne, M.C.,
Tanaka, T., E. Duan, Fisher, S. J., Liao, J, Chen, J., and Wang, F. mTOR Supports Long-Term SelfRenewal and Suppresses Mesoderm and Endoderm Activities of Human Embryonic Stem Cells.
2009. Proc. Natl Acad. Sci. 106(19): 7849-5. Epub 2009 Apr 28.
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