|Budget Amount *help
¥16,200,000 (Direct Cost : ¥16,200,000)
Fiscal Year 1998 : ¥3,600,000 (Direct Cost : ¥3,600,000)
Fiscal Year 1997 : ¥12,600,000 (Direct Cost : ¥12,600,000)
phd1^+, the first histone deacetylase gene from fission yeast Schizosaccharomyces pombe, was cloned. The gene was required for the onset of meiotic cell cycle and resistance to trichostatin A (TSA), a histone deacetylase inhibitor. RT-PCR and Western blot analyses revealed that p2lWaf1, a cyclin-dependent kinase inhibitor, was induced in mammalian cells in response to TSA.The enhanced expression was independent of p53, a major tumor suppressor protein, suggesting that p21 induction is responsible for TSA-induced cell cycle arrest. A human homolog of ORM1, the target protein of leptomycin B (LMB), was cloned. We showed that CRM1 is a receptor for the nuclear export signal (NES) of proteins, and that LMB directly binds CRM1 to inhibit its function. Using LMB, we demonstrated that Pap1, a fission yeast AP-1 like transcription factor, contained NES in the C-terminal region, which is responsible for its cytoplasmic localization.