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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.

PLIP, a Novel Splice Variant of Tip60, Interacts with Group IV Cytosolic Phospholipase A2, Induces Apoptosis, and Potentiates Prostaglandin Production

Alice M. Sheridan,* Thomas Force, Hyung-Jin Yoon, Eileen O'Leary, Gabriel Choukroun, M. Reza Taheri, and Joseph V. Bonventre

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.

* Corresponding author. Mailing address: Massachusetts General Hospital, 149-4002 13th St., Charlestown, MA 02129-2060. Phone: (617) 724-9688. Fax: (617) 726-4356. E-mail: asheridan{at}partners.org.

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.


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