Screening of phosphatidylinositol turnover inhibitors and regulation of cell cycle progression

K. Umezawa, A. Deguchi, Masaya Imoto

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)1578-1584
Number of pages7
JournalJapanese Journal of Cancer and Chemotherapy
Volume24
Issue number11
Publication statusPublished - 1997

Fingerprint

Phosphatidylinositols
CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase
Cell Cycle
Phosphotransferases
Streptomyces
Type C Phospholipases
Serum
S Phase
Cyclin G1
Cyclin D
Cyclin E
Porifera
Enzymes
Cultured Cells
Phosphorylation
inostamycin
Growth

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 journalArticle

@article{dd3111b63b504f65b4db2a597d92bf63,
title = "Screening of phosphatidylinositol turnover inhibitors and regulation of cell cycle progression",
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.",
keywords = "Inostamycin, Phosphatidylinositol synthase, RB protein",
author = "K. Umezawa and A. Deguchi and Masaya Imoto",
year = "1997",
language = "English",
volume = "24",
pages = "1578--1584",
journal = "Japanese Journal of Cancer and Chemotherapy",
issn = "0385-0684",
publisher = "Japanese Journal of Cancer and Chemotherapy Publishers Inc.",
number = "11",

}

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

UR - http://www.scopus.com/inward/record.url?scp=0030735157&partnerID=8YFLogxK

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 -