Manipulating the onset of cell cycle withdrawal in differentiated erythroid cells with cyclin-dependent kinases and inhibitors

Igor Matushansky, Farshid Radparvar, Arthur I. Skoultchi

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Terminal differentiation of erythroid cells results in terminal cell divisions followed by irreversible cell cycle withdrawal of hemoglobanized cells. The mechanisms leadlng to cell cycle withdrawal were assessed in stable transfectants of mutine erythroleukemia cells, in which the activiries of cyclin-dependent kinases (CDKs) and CDK inhibitors (CDKIs) could be tightly regulated during differentiation. Cell cycle withdrawal of differentiating cells is medlated by induction of several CDKIs, thereby leading to inhibition of CDK2 and CDK4. Manipulation of CDK activity in differentiating cells demonstrates that the onset of cell cycle withdrawal can be either greatly accelerated or greatly delayed without affecting hemoglobln levels. Extending the proliferation of differentiating cells requires the synergisfic action of CDK2 and CDK4. Importantly, CDK6 cannot substitute for CDK4 in this role, which demonstrates that the 2 cyclin D-dependent kinases are funcfionally different. The results show that differentiating hemoglobinized cells can be made to proliferate far beyond their normal capacity to divide. (C) 2000 by The Amerlcan Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2755-2764
Number of pages10
JournalBlood
Volume96
Issue number8
StatePublished - Oct 15 2000

Fingerprint

Erythroid Cells
Cyclin-Dependent Kinases
Cell Cycle
Cells
Cyclin-Dependent Kinase 2
Cyclin D
Leukemia, Erythroblastic, Acute
Hematology
Cell Division
Cell Proliferation
Phosphotransferases

ASJC Scopus subject areas

  • Hematology

Cite this

Manipulating the onset of cell cycle withdrawal in differentiated erythroid cells with cyclin-dependent kinases and inhibitors. / Matushansky, Igor; Radparvar, Farshid; Skoultchi, Arthur I.

In: Blood, Vol. 96, No. 8, 15.10.2000, p. 2755-2764.

Research output: Contribution to journalArticle

@article{bea09ce411a4499fb28f8ff15056f73c,
title = "Manipulating the onset of cell cycle withdrawal in differentiated erythroid cells with cyclin-dependent kinases and inhibitors",
abstract = "Terminal differentiation of erythroid cells results in terminal cell divisions followed by irreversible cell cycle withdrawal of hemoglobanized cells. The mechanisms leadlng to cell cycle withdrawal were assessed in stable transfectants of mutine erythroleukemia cells, in which the activiries of cyclin-dependent kinases (CDKs) and CDK inhibitors (CDKIs) could be tightly regulated during differentiation. Cell cycle withdrawal of differentiating cells is medlated by induction of several CDKIs, thereby leading to inhibition of CDK2 and CDK4. Manipulation of CDK activity in differentiating cells demonstrates that the onset of cell cycle withdrawal can be either greatly accelerated or greatly delayed without affecting hemoglobln levels. Extending the proliferation of differentiating cells requires the synergisfic action of CDK2 and CDK4. Importantly, CDK6 cannot substitute for CDK4 in this role, which demonstrates that the 2 cyclin D-dependent kinases are funcfionally different. The results show that differentiating hemoglobinized cells can be made to proliferate far beyond their normal capacity to divide. (C) 2000 by The Amerlcan Society of Hematology.",
author = "Igor Matushansky and Farshid Radparvar and Skoultchi, {Arthur I.}",
year = "2000",
month = "10",
day = "15",
language = "English (US)",
volume = "96",
pages = "2755--2764",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "8",

}

TY - JOUR

T1 - Manipulating the onset of cell cycle withdrawal in differentiated erythroid cells with cyclin-dependent kinases and inhibitors

AU - Matushansky, Igor

AU - Radparvar, Farshid

AU - Skoultchi, Arthur I.

PY - 2000/10/15

Y1 - 2000/10/15

N2 - Terminal differentiation of erythroid cells results in terminal cell divisions followed by irreversible cell cycle withdrawal of hemoglobanized cells. The mechanisms leadlng to cell cycle withdrawal were assessed in stable transfectants of mutine erythroleukemia cells, in which the activiries of cyclin-dependent kinases (CDKs) and CDK inhibitors (CDKIs) could be tightly regulated during differentiation. Cell cycle withdrawal of differentiating cells is medlated by induction of several CDKIs, thereby leading to inhibition of CDK2 and CDK4. Manipulation of CDK activity in differentiating cells demonstrates that the onset of cell cycle withdrawal can be either greatly accelerated or greatly delayed without affecting hemoglobln levels. Extending the proliferation of differentiating cells requires the synergisfic action of CDK2 and CDK4. Importantly, CDK6 cannot substitute for CDK4 in this role, which demonstrates that the 2 cyclin D-dependent kinases are funcfionally different. The results show that differentiating hemoglobinized cells can be made to proliferate far beyond their normal capacity to divide. (C) 2000 by The Amerlcan Society of Hematology.

AB - Terminal differentiation of erythroid cells results in terminal cell divisions followed by irreversible cell cycle withdrawal of hemoglobanized cells. The mechanisms leadlng to cell cycle withdrawal were assessed in stable transfectants of mutine erythroleukemia cells, in which the activiries of cyclin-dependent kinases (CDKs) and CDK inhibitors (CDKIs) could be tightly regulated during differentiation. Cell cycle withdrawal of differentiating cells is medlated by induction of several CDKIs, thereby leading to inhibition of CDK2 and CDK4. Manipulation of CDK activity in differentiating cells demonstrates that the onset of cell cycle withdrawal can be either greatly accelerated or greatly delayed without affecting hemoglobln levels. Extending the proliferation of differentiating cells requires the synergisfic action of CDK2 and CDK4. Importantly, CDK6 cannot substitute for CDK4 in this role, which demonstrates that the 2 cyclin D-dependent kinases are funcfionally different. The results show that differentiating hemoglobinized cells can be made to proliferate far beyond their normal capacity to divide. (C) 2000 by The Amerlcan Society of Hematology.

UR - http://www.scopus.com/inward/record.url?scp=0034667668&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034667668&partnerID=8YFLogxK

M3 - Article

VL - 96

SP - 2755

EP - 2764

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -