ASSOCIATION OF PHOSPHORYLATED SERINE ARGININE (SR) SPLICING FACTORS WITH THE U1-SMALL RIBONUCLEOPROTEIN (SNRNP) AUTOANTIGEN COMPLEX ACCOMPANIES APOPTOTIC CELL-DEATH/
Pj. Utz et al., ASSOCIATION OF PHOSPHORYLATED SERINE ARGININE (SR) SPLICING FACTORS WITH THE U1-SMALL RIBONUCLEOPROTEIN (SNRNP) AUTOANTIGEN COMPLEX ACCOMPANIES APOPTOTIC CELL-DEATH/, The Journal of experimental medicine, 187(4), 1998, pp. 547-560
Proteins subject to proteolysis or phosphorylation during apoptosis ar
e commonly precipitated by autoantibodies found in the serum of patien
ts with systemic lupus erythematosus (SLE). We screened a panel of mur
ine monoclonal and human monospecific sera reactive with known autoant
igens for their ability to selectively precipitate phosphoproteins fro
m apoptotic Jurkat T cell lysates. Sera known to recognize the U1-smal
l nuclear ribonucleoprotein (snRNP) complex (confirmed by their abilit
y to precipitate U1-snRNA) selectively precipitated a phosphoprotein c
omplex (pp54, pp42, py34, and pp23) from apoptotic lysates. Monoclonal
antibodies reactive with U1-snRNP proteins precipitated the same phos
phoprotein complex from apoptotic lysates. The phosphorylation and/or
recruitment of these proteins to the U1-snRNP complex is induced by mu
ltiple apoptotic stimuli (e.g., Fas ligation, gamma irradiation or UV
irradiation), and is blocked by overexpression of bcl-2. The U1-snRNP-
associated phosphoprotein complex is immunoprecipitated by monoclonal
antibodies reactive with serine/arginine (SR) proteins that comprise a
structurally related family of splicing factors. The association of p
hosphorylated SR proteins with the U1-snRNP complex in cells undergoin
g apoptosis suggests a mechanism for regulation of alternative splicin
g of apoptotic effector molecules.