Molecular and Cellular Biology, July 2001, p. 4470-4481, Vol. 21, No. 14
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.14.4470-4481.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Medical Services, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Charlestown, Massachusetts 02129
Received 20 March 2000/Returned for modification 25 April 2000/Accepted 28 March 2001
The group IV cytosolic phospholipase A2
(cPLA2) has been localized to the nucleus (M. R. Sierra-Honigmann, J. R. Bradley, and J. S. Pober, Lab.
Investig. 74:684-695, 1996) and is known to translocate from the
cytosolic compartment to the nuclear membrane (S. Glover, M. S. de
Carvalho, T. Bayburt, M. Jonas, E. Chi, C. C. Leslie, and M. H. Gelb, J. Biol. Chem. 270:15359-15367, 1995; A. R. Schievella, M. K. Regier, W. L. Smith, and L. L. Lin,
J. Biol. Chem. 270:30749-30754, 1995). We hypothesized that
nuclear proteins interact with cPLA2 and participate in the
functional effects of this translocation. We have identified a nuclear
protein, cPLA2-interacting protein (PLIP), a splice variant
of human Tip60, which interacts with the amino terminal region of
cPLA2. Like Tip60, PLIP cDNA includes the MYST domain
containing a C2HC zinc finger and well-conserved similarities to
acetyltransferases. Both PLIP and Tip60 coimmunoprecipitate and
colocalize with cPLA2 within the nuclei of transfected COS
cells. A polyclonal antibody raised to PLIP recognizes both PLIP and
Tip60. Endogenous Tip60 and/or PLIP in rat mesangial cells is localized
to the nucleus in response to serum deprivation. Nuclear localization
coincides temporally with apoptosis. PLIP expression, mediated by
adenoviral gene transfer, potentiates serum deprivation-induced
prostaglandin E2 (PGE2) production and
apoptosis in mouse mesangial cells from cPLA2+/+ mice but not in mesangial cells
derived from cPLA2
/
mice. Thus PLIP, a
splice variant of Tip60, interacts with cPLA2 and
potentiates cPLA2-mediated PGE2 production and apoptosis.
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