Expression of G1 cyclins and cyclin-dependent kinase-2 activity during terminal differentiation of cultured human trophoblast

Pamela P. McKenzie, James S. Foster, Scott House, Antonine Bukovsky, Michael Caudle, Jay Wimalasena

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Cyclin-dependent kinases (Cdks) and their cyclin partners regulate mammalian cell proliferation and withdrawal from the cell cycle and, as such, control differentiation in many tissues. Studies were undertaken to examine the roles of cell cycle proteins in differentiating cytotrophoblasts. Cyclin E gene and protein expression was down-regulated after 24 h in cultured trophoblasts. Cdk2-associated kinase activity was decreased after 96 h in culture as was the amount of cyclin E in complexes with Cdk2; however, levels of the Cdk inhibitor, p27(Kip1), were significantly increased. In freshly isolated trophoblasts and in 24-h cultures, the retinoblastoma gene product (pRb) was found in both the active and inactive forms, yet only hypophosphorylated, active pRb was present in syncytiotrophoblast. Thus, inactivation of Cdk2 through cyclin E down-regulation and increased p27(Kip1) expression leads to an accumulation of active pRb in syncytiotrophoblast. Prevention of entry into S phase by hypophosphorylated pRb may allow trophoblasts to respond to signals that potentiate differentiation. Our studies suggest that regulation of G1-phase Cdk activity may be involved in the terminal differentiation process of cytotrophoblasts.

Original languageEnglish (US)
Pages (from-to)1283-1289
Number of pages7
JournalBiology of Reproduction
Volume58
Issue number5
DOIs
StatePublished - May 1 1998
Externally publishedYes

Fingerprint

Cyclin G1
Cyclin-Dependent Kinase 2
Trophoblasts
Cyclin E
Retinoblastoma Genes
Cell Cycle Proteins
Cyclins
Cyclin-Dependent Kinases
G1 Phase
S Phase
Cell Cycle
Phosphotransferases
Down-Regulation
Cell Proliferation
Gene Expression

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Expression of G1 cyclins and cyclin-dependent kinase-2 activity during terminal differentiation of cultured human trophoblast. / McKenzie, Pamela P.; Foster, James S.; House, Scott; Bukovsky, Antonine; Caudle, Michael; Wimalasena, Jay.

In: Biology of Reproduction, Vol. 58, No. 5, 01.05.1998, p. 1283-1289.

Research output: Contribution to journalArticle

McKenzie, Pamela P. ; Foster, James S. ; House, Scott ; Bukovsky, Antonine ; Caudle, Michael ; Wimalasena, Jay. / Expression of G1 cyclins and cyclin-dependent kinase-2 activity during terminal differentiation of cultured human trophoblast. In: Biology of Reproduction. 1998 ; Vol. 58, No. 5. pp. 1283-1289.
@article{ec865d015da14079808ecc3c1e55c53a,
title = "Expression of G1 cyclins and cyclin-dependent kinase-2 activity during terminal differentiation of cultured human trophoblast",
abstract = "Cyclin-dependent kinases (Cdks) and their cyclin partners regulate mammalian cell proliferation and withdrawal from the cell cycle and, as such, control differentiation in many tissues. Studies were undertaken to examine the roles of cell cycle proteins in differentiating cytotrophoblasts. Cyclin E gene and protein expression was down-regulated after 24 h in cultured trophoblasts. Cdk2-associated kinase activity was decreased after 96 h in culture as was the amount of cyclin E in complexes with Cdk2; however, levels of the Cdk inhibitor, p27(Kip1), were significantly increased. In freshly isolated trophoblasts and in 24-h cultures, the retinoblastoma gene product (pRb) was found in both the active and inactive forms, yet only hypophosphorylated, active pRb was present in syncytiotrophoblast. Thus, inactivation of Cdk2 through cyclin E down-regulation and increased p27(Kip1) expression leads to an accumulation of active pRb in syncytiotrophoblast. Prevention of entry into S phase by hypophosphorylated pRb may allow trophoblasts to respond to signals that potentiate differentiation. Our studies suggest that regulation of G1-phase Cdk activity may be involved in the terminal differentiation process of cytotrophoblasts.",
author = "McKenzie, {Pamela P.} and Foster, {James S.} and Scott House and Antonine Bukovsky and Michael Caudle and Jay Wimalasena",
year = "1998",
month = "5",
day = "1",
doi = "10.1095/biolreprod58.5.1283",
language = "English (US)",
volume = "58",
pages = "1283--1289",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "5",

}

TY - JOUR

T1 - Expression of G1 cyclins and cyclin-dependent kinase-2 activity during terminal differentiation of cultured human trophoblast

AU - McKenzie, Pamela P.

AU - Foster, James S.

AU - House, Scott

AU - Bukovsky, Antonine

AU - Caudle, Michael

AU - Wimalasena, Jay

PY - 1998/5/1

Y1 - 1998/5/1

N2 - Cyclin-dependent kinases (Cdks) and their cyclin partners regulate mammalian cell proliferation and withdrawal from the cell cycle and, as such, control differentiation in many tissues. Studies were undertaken to examine the roles of cell cycle proteins in differentiating cytotrophoblasts. Cyclin E gene and protein expression was down-regulated after 24 h in cultured trophoblasts. Cdk2-associated kinase activity was decreased after 96 h in culture as was the amount of cyclin E in complexes with Cdk2; however, levels of the Cdk inhibitor, p27(Kip1), were significantly increased. In freshly isolated trophoblasts and in 24-h cultures, the retinoblastoma gene product (pRb) was found in both the active and inactive forms, yet only hypophosphorylated, active pRb was present in syncytiotrophoblast. Thus, inactivation of Cdk2 through cyclin E down-regulation and increased p27(Kip1) expression leads to an accumulation of active pRb in syncytiotrophoblast. Prevention of entry into S phase by hypophosphorylated pRb may allow trophoblasts to respond to signals that potentiate differentiation. Our studies suggest that regulation of G1-phase Cdk activity may be involved in the terminal differentiation process of cytotrophoblasts.

AB - Cyclin-dependent kinases (Cdks) and their cyclin partners regulate mammalian cell proliferation and withdrawal from the cell cycle and, as such, control differentiation in many tissues. Studies were undertaken to examine the roles of cell cycle proteins in differentiating cytotrophoblasts. Cyclin E gene and protein expression was down-regulated after 24 h in cultured trophoblasts. Cdk2-associated kinase activity was decreased after 96 h in culture as was the amount of cyclin E in complexes with Cdk2; however, levels of the Cdk inhibitor, p27(Kip1), were significantly increased. In freshly isolated trophoblasts and in 24-h cultures, the retinoblastoma gene product (pRb) was found in both the active and inactive forms, yet only hypophosphorylated, active pRb was present in syncytiotrophoblast. Thus, inactivation of Cdk2 through cyclin E down-regulation and increased p27(Kip1) expression leads to an accumulation of active pRb in syncytiotrophoblast. Prevention of entry into S phase by hypophosphorylated pRb may allow trophoblasts to respond to signals that potentiate differentiation. Our studies suggest that regulation of G1-phase Cdk activity may be involved in the terminal differentiation process of cytotrophoblasts.

UR - http://www.scopus.com/inward/record.url?scp=0031596836&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031596836&partnerID=8YFLogxK

U2 - 10.1095/biolreprod58.5.1283

DO - 10.1095/biolreprod58.5.1283

M3 - Article

VL - 58

SP - 1283

EP - 1289

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 5

ER -