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Frank
Luca, Ph.D.
Assistant Professor, Dept of Animal Biology
Cell
Biology and Physiology Program
Address
School of Veterinary Medicine
Room 154E
3800 Spruce St
Philadelphia, PA 19104
Office tel.: 215 573-5664
Lab tel.: 215 573-5665
Fax: 215 573-5188
E-mail: fluca@vet.upenn.edu
EDUCATION
Boston University: BA (Biology), 1983.
Duke University: PhD (Cell Biology and Genetics), 1992.
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RESEARCH
INTERESTS
Yeast and mammalian cell cycle regulation; Regulation of
mitotic exit, cytokinesis, daughter cell-specific gene expression,
and polarized growth.
Key
words: yeast, cell cycle, mitosis, cytokinesis,
cell polarity, daughter cell-specific gene expression, mitotic
checkpoint regulation, kinetochore, Mitotic Exit Network (MEN),
Regulation of Ace2-dependent transcription and Morphogenesis
(RAM).
Search PubMed for articles
DESCRIPTION
OF RESEARCH
The Luca lab studies conserved signaling networks that coordinate
the diverse cellular processes associated with cell division
and cellular morphogenesis. The lab employs multidisciplinary
approaches, including yeast genetics, biochemistry and cellular
and molecular biology to investigate the conserved functions
of the Mob protein family. The budding yeast Saccharomyces
cerevisiae expresses two Mob proteins, Mob1 and Mob2, that
function in distinct pathways.
Mob1 and MEN
Mob1 is a component of the conserved Mitotic Exit Network
(MEN), which coordinates events associated with the M to G1
transition, such as cyclin dependent kinase (CDK) inactivation,
spindle disassembly, cytokinesis and G1 gene transcription.
Mob1 is a regulatory subunit of the MEN protein kinase Dbf2,
which is related to the poorly understood human LATS tumor
suppressor. Both Mob1 and Dbf2 localize to mitotic spindle
poles and the cytokinesis ring during mitotic exit. Mob1 and
Dbf2 kinase appear to mediate mitotic exit by activating Cdc14
phosphatase, which antagonizes the mitosis inducing activity
of CDK. In addition, Mob1 and Dbf2 are important for triggering
cytokinesis and septum formation. Intriguingly, Mob1 also
interacts with Mps1 kinase, which regulates mitotic checkpoint
function and centrosome duplication. Currently, we are trying
to establish how Mob1-Dbf2 kinase regulates Cdc14 phosphatase
and cytokinesis. We are also exploring the functional significance
of the Mob1-Mps1 interaction.
Mob2 and RAM
We recently discovered that Mob2 is a component of a conserved
signaling network, termed RAM for Regulation of Ace2-dependent
transcription and Morphogenesis. The RAM network is comprised
of at least six proteins that regulate: 1) polarized growth
by maintaining the polarity of the actin cytoskeleton; 2)
the localization and activity of Ace2 transcription factor,
which regulates transcription of a subset of genes in the
daughter cell; and 3) maintenance of cell wall integrity.
Mob2 binds to and regulates Cbk1, a Dbf2-related protein kinase.
Both Mob2 and Cbk1 localize to sites of cortical growth and,
remarkably, to the daughter cell nucleus. Our data suggests
that the Mob2-Cbk1 complex acts late in the RAM signaling
network and directly regulates the daughter cell-specific
localization and function of Ace2 transcription factor. Thus,
the RAM signaling network provides a novel mechanism for yeast
cells to regulate differential gene expression. This work
has important implications regarding mechanisms for controlling
development in multicellular organisms. We are currently investigating
the mechanisms of RAM in regulating polarized growth and daughter-specific
gene expression.
Mammalian MEN and RAM
Because most MEN and RAM proteins are highly conserved, we
expect that MEN- and RAM-like signaling networks will be critical
for regulating cell division and development in all eukaryotes.
Thus, in addition to exploring the functions of MEN and RAM
signaling networks in yeast, we are expanding our research
to investigate the roles of related signaling networks in
mammalian cells. Collectively, research regarding Mobs, MEN
and RAM will help resolve the regulatory mechanisms of cell
division and cancer development.
RECENT
PUBLICATIONS
Weiss, E.L., Kurischko, C., Zhang, C., Shokat, K., Drubin,
D.G. and Luca, F.C. (2002) The Saccharomyces cerevisiae Mob2p-Cbk1p
kinase complex promotes polarized growth and acts with the
mitotic exit network to facilitate daughter cell-specific
localization of Ace2p transcription factor. J. Cell Biol.
158: 885 – 900
Nelson, B., Kurischko, C., Horecka, J., Mody, M., Nair, P.,
Pratt, P., Zougman, A., McBroom, L., Hughes, T.R., Boone,
C., Luca, F.C. (2003). RAM: a Conserved Signaling Network
that Regulates Ace2p Transcriptional Activity and Polarized
Morphogenesis. Mol. Biol. Cell 14:3782–3803
Stavridi, E.S., Harris, K.G., Huyen, Y., Verwoerd, P., Stayrook,
S.E., Pavletich, N.P., Jeffrey, P.D. and Luca F.C. (2003)
Crystal structure of human Mob1 protein; toward understanding
Mob-regulated cell cycle pathways. Structure 11:1163–1170.
Bembenek, J., Kang, J., Kurischko, C., Li, B., Raab, J.R.,
Belanger, K.D., Luca, F.C., Yu, H. (2005) Crm1-Mediated Nuclear
Export of Cdc14 is Required for the Completion of Cytokinesis
in Budding Yeast. Cell Cycle 4:961-971
Kurischko, C., Weiss, G., Ottey, M.A., Luca F.C. (2005) A
role for the conserved Saccharomyces cerevisiae RAM signaling
network in cell integrity. Genetics. In press
Bothos, J., Tuttle, R.L., Ottey, M., Luca, F.C., Halazonetis,
T.D. (2005) Human LATS1 is a mitotic exit network kinase.
Cancer Research. In press
Lab
ROTATION
PROJECTS FOR 2006-2007
Many rotation projects are available involving a variety
of approaches. Some examples are:
- Investigate the role of MEN and RAM in regulating cytokinesis,
cell polarity, genomic stability and gene expression.
- Genetic and biochemical approaches to identify regulators
and substrates of MEN and RAM.
- Characterization of MEN and RAM protein complexes
- Structure-function analysis of Mob proteins and interacting
kinases.
- Analysis of MEN or RAM protein dynamics in live cells
by fluorescence recovery after photobleaching (FRAP).
- Identification and characterization of mammalian MEN
and RAM networks.
- Lab
personnel:
- Cornelia Kurischko, Ph.D. - Research Specialist
Michelle Ottey, Ph.D. - Postdoctoral Fellow
Pavel Nazarov, Ph.D. - Postdoctoral Fellow
Zach Kern - Undergraduate research assistant
Diane Raines - Lab assistant
last updated 7/2005
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