R. Weisman et al., A MULTICOPY SUPPRESSOR OF A CELL-CYCLE DEFECT IN SCHIZOSACCHAROMYCES-POMBE ENCODES A HEAT SHOCK-INDUCIBLE 40 KDA CYCLOPHILIN-LIKE PROTEIN, EMBO journal, 15(3), 1996, pp. 447-456
Cyclophilins are peptidyl-prolyl cis-trans isomerases (PPIases) which
have been implicated in intracellular protein folding, transport and a
ssembly. Cyclophilins are also known as the intracellular receptors fo
r the immunosuppressive drug cyclosporin A (CsA), The most common type
of cyclophilins are the 18 kDa cytosolic proteins containing only the
highly conserved core domain for PPIase and CsA binding activities, T
he wis2(+) gene of the fission yeast Schizosaccharomyces pombe was iso
lated as a multicopy suppressor of wee1-50 cdc25-22 win1-1, a triple m
utant strain which exhibits a cell cycle defect phenotype. Sequence an
alysis of wis2(+) reveals that it encodes a 40 kDa cyclophilin-like pr
otein, homologous to the mammalian cyclophilin 40. The 18 kDa cyclophi
lin domain (CyP-18) of wis2 is followed by a C-terminal region of 188
amino acids, The C-terminal region of wis2 is essential for suppressio
n of the triple mutant defect, Furthermore, this region of the protein
is able to confer suppression activity on the 18 kDa S.pombe cyclophi
lin, cyp1, since a hybrid protein consisting of an 18 kDa S.pombe cycl
ophilin (cyp1) fused to the C-terminus of wis2 shows suppression activ
ity, We also demonstrate that the level of wis2(+) mRNA increases 10-
to 20-fold upon heat shock of S.pombe cells, suggesting a role for wis
2(+) in the heat-shock response.