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Sheridan, AM, Force, T, Yoon, HJ, O'Leary, E, Choukroun, G, Taheri, MR and Bonventre, JV (2001) PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production. Mol. Cell. Biol. 21:4470-81
The group IV cytosolic phospholipase A(2) (cPLA(2)) 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 cPLA(2) and participate in the functional effects of this translocation. We have identified a nuclear protein, cPLA(2)-interacting protein (PLIP), a splice variant of human Tip60, which interacts with the amino terminal region of cPLA(2). 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 cPLA(2) 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 E(2) (PGE(2)) production and apoptosis in mouse mesangial cells from cPLA(2)(+/+) mice but not in mesangial cells derived from cPLA(2)(-/-) mice. Thus PLIP, a splice variant of Tip60, interacts with cPLA(2) and potentiates cPLA(2)-mediated PGE(2) production and apoptosis.
Acetyltransferases/metabolism; Alternative Splicing; Amino Acid Sequence; Animals; Apoptosis; Base Sequence; COS Cells; Cell Line; Cell Nucleus/metabolism; Cercopithecus aethiops; Culture Media, Serum-Free; DNA, Complementary; Dinoprostone/biosynthesis; Group IV Phospholipases A2; Histone Acetyltransferases; Humans; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Phospholipases A/genetics; Phospholipases A/metabolism; Precipitin Tests; Rats; Tissue Distribution; Zinc Fingers