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Faculty
Maurice B. Feinstein
Professor of Cell Biology
feinstein@nso1.uchc.edu
- B.S., Columbia University
- M.S., Columbia University
- Ph.D., State University of New York Health Science Center
- Cell Biology Graduate
Program
- Not accepting students for Lab Rotations at this time
Areas of Interest:
My current research focus concerns the study of a gene discovered in
my lab which we term CHERP, i.e., Calcium Homeostasis Endoplasmic
Reticulum Protein. The cDNA for this protein was cloned and
sequenced from an HEL cell cDNA expression library using monoclonal
antibody to a human platelet ER membrane constituent. Using FISH, the
gene was localized to chromosome 19 p13.1. An adenoviral vector was
constructed that permitted regulated expression of nearly full length
CHERP protein and a subsequent severe impairment of the ability of the
cells to mobilize Ca2+ when appropriately stimulated. Immunofluorescence
microscopy revealed that CHERP was co-localized with the two
intracellular Ca2+ channels that are present in the ER/SR of cells, i.e.
the InsP3-receptor and the ryanodine receptor. The cells we studied were
human neoplastic cell lines, and their rapid rates of proliferation were
sharply reduced by depletion of CHERP. Furthermore, in Jurkat T-cells
the depletion of CHERP impaired the Ca2+- dependent nuclear
translocation of the key transcription factor NFAT which is important
for T-cell proliferation and differentiation. Current studies are
focused on the effects of CHERP knockdown on the functional properties
of cultured cardiac muscle cells and neuroblastoma cells. Since our
first discovery, several groups have found the same protein in human
tissues and in rodents by cloning or by computer analysis of the
genomes. Protein sequences with varying degrees of sequence homology to
CHERP have been identified in the genomes of C. elegans, Drosophila
and zebra fish. The amino acid sequence of human CHERP is unique,
although it contains several putative domains found in other proteins
that function in interactions with RNA and RNA polymerase II. This has
led to proposal of an alternative name, SCAF6, i.e., spiceosome
associated factor 6. It was proposed that SCAF6 has a domain that binds
to RNA pol II, and could be involved in mRNA splicing and synthesis.
However, we do not find localization of CHERP in the nuclei of cells
where RNA pol II is predominantly found. Current studies in our lab
using siRNA and morpholino oligos to knockdown CHERP are in progress in
order to determine the functional roles for this protein in cardiac
muscle.
Selected Publications:
O'Rourke FA, LaPlante JM, Feinstein MB. 2003. Antisense-mediated loss
of calcium homoeostasis endoplasmic reticulum protein (CHERP;
ERPROT213-21) impairs Ca2+ mobilization, nuclear factor of activated
T-cells (NFAT) activation and cell proliferation in Jurkat
T-lymphocytes. Biochem J. Jul 1;373(Pt 1):133-43.
Laplante JM, O'Rourke F, Lu X, Fein A, Olsen A, Feinstein MB. 2000.
Cloning of human Ca2+ homoeostasis endoplasmic reticulum protein (CHERP):
regulated expression of antisense cDNA depletes CHERP, inhibits
intracellular Ca2+ mobilization and decreases cell proliferation.
Biochem J. May 15;348 Pt 1:189-99.
Lu X, Fein A, Feinstein MB, O'Rourke FA. 1999. Antisense knock out of
the inositol 1,3,4,5-tetrakisphosphate receptor GAP1(IP4BP) in the human
erythroleukemia cell line leads to the appearance of intermediate
conductance K(Ca) channels that hyperpolarize the membrane and enhance
calcium influx. J Gen Physiol. Jan;113(1):81-96.
Armando P. Signore, Flavia O'Rourke, Xinghua Lu, Maurice B.
Feinstein, andHermes H. Yeh (1999) Immunohistochemical localization of
the InsP4 receptor GTP-ase activating protein GAP1IP4BP in the rat
brain. J. NeuroscienceResearch 55: 321-328. |
