Abstract
Phosphatidylinositol (PI) turnover is considered to be involved in the regulation of cell growth. The enzymes for PI turnover include phospholipase C (PLC), PI4-kinase and PI synthase. We have isolated pholipeptin and fluvirucin B2 from microorganisms and akaterpin from a marine sponge as PLC γ inhibitors. We also isolated echiguanines from Streptomyces as P14-kinase inhibitors. Since echiguanines did not inhibit the enzyme in situ, we synthesized their ribosylated derivatives that were effective in cultured cells. We previously isolated inostamycin from Streptomyces as an inhibitor of PI synthase. We found that inostamycin induced G1 block in cycling NRK cells. Inostamycin inhibited the serum-induced S-phase induction in quiescent NRK cells. Inostamycin was found to decrease serum-induced expression of cyclin D and cyclin E, without inhibiting the activation of MAP kinase. It also inhibited serum-induced activation of CDK2 and phosphorylation of pRB. Thus, PI synthesis was suggested to be involved in regulation of serum- induced S-phase induction by modulating G1 cyclin expression.
| Original language | English |
|---|---|
| Pages (from-to) | 1578-1584 |
| Number of pages | 7 |
| Journal | Japanese Journal of Cancer and Chemotherapy |
| Volume | 24 |
| Issue number | 11 |
| Publication status | Published - 1997 |
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Keywords
- Inostamycin
- Phosphatidylinositol synthase
- RB protein
ASJC Scopus subject areas
- Cancer Research
- Pharmacology
Cite this
Screening of phosphatidylinositol turnover inhibitors and regulation of cell cycle progression. / Umezawa, K.; Deguchi, A.; Imoto, Masaya.
In: Japanese Journal of Cancer and Chemotherapy, Vol. 24, No. 11, 1997, p. 1578-1584.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Screening of phosphatidylinositol turnover inhibitors and regulation of cell cycle progression
AU - Umezawa, K.
AU - Deguchi, A.
AU - Imoto, Masaya
PY - 1997
Y1 - 1997
N2 - Phosphatidylinositol (PI) turnover is considered to be involved in the regulation of cell growth. The enzymes for PI turnover include phospholipase C (PLC), PI4-kinase and PI synthase. We have isolated pholipeptin and fluvirucin B2 from microorganisms and akaterpin from a marine sponge as PLC γ inhibitors. We also isolated echiguanines from Streptomyces as P14-kinase inhibitors. Since echiguanines did not inhibit the enzyme in situ, we synthesized their ribosylated derivatives that were effective in cultured cells. We previously isolated inostamycin from Streptomyces as an inhibitor of PI synthase. We found that inostamycin induced G1 block in cycling NRK cells. Inostamycin inhibited the serum-induced S-phase induction in quiescent NRK cells. Inostamycin was found to decrease serum-induced expression of cyclin D and cyclin E, without inhibiting the activation of MAP kinase. It also inhibited serum-induced activation of CDK2 and phosphorylation of pRB. Thus, PI synthesis was suggested to be involved in regulation of serum- induced S-phase induction by modulating G1 cyclin expression.
AB - Phosphatidylinositol (PI) turnover is considered to be involved in the regulation of cell growth. The enzymes for PI turnover include phospholipase C (PLC), PI4-kinase and PI synthase. We have isolated pholipeptin and fluvirucin B2 from microorganisms and akaterpin from a marine sponge as PLC γ inhibitors. We also isolated echiguanines from Streptomyces as P14-kinase inhibitors. Since echiguanines did not inhibit the enzyme in situ, we synthesized their ribosylated derivatives that were effective in cultured cells. We previously isolated inostamycin from Streptomyces as an inhibitor of PI synthase. We found that inostamycin induced G1 block in cycling NRK cells. Inostamycin inhibited the serum-induced S-phase induction in quiescent NRK cells. Inostamycin was found to decrease serum-induced expression of cyclin D and cyclin E, without inhibiting the activation of MAP kinase. It also inhibited serum-induced activation of CDK2 and phosphorylation of pRB. Thus, PI synthesis was suggested to be involved in regulation of serum- induced S-phase induction by modulating G1 cyclin expression.
KW - Inostamycin
KW - Phosphatidylinositol synthase
KW - RB protein
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UR - http://www.scopus.com/inward/citedby.url?scp=0030735157&partnerID=8YFLogxK
M3 - Article
C2 - 9309157
AN - SCOPUS:0030735157
VL - 24
SP - 1578
EP - 1584
JO - Japanese Journal of Cancer and Chemotherapy
JF - Japanese Journal of Cancer and Chemotherapy
SN - 0385-0684
IS - 11
ER -