Effects of iron-depletion on cell cycle progression in normal human T lymphocytes: Selective inhibition of the appearance of the cyclin A-associated component of the p33cdk2 kinase

Joseph J. Lucas, Agota Szepesi, Joanne Domenico, Kozo Takase, A. Tordai, Naohiro Terada, Erwin W. Gelfand

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Iron removal by the chelating-agent deferoxamine (DFO) arrests cell cycle progression of activated human T cells in late G1 phase, before the G1/S border. The effects of the drug on molecules that regulate progression through the cell cycle were defined. DFO (10 μmol/L) inhibited induction of transcription of the cdc2 gene, but had no effect on accumulation of cdk2, cdk4, or interleukin (IL)-Z transcripts. No detectable p34cdc2 protein accumulated, but synthesis of the p33cdk2 protein was begun. It accumulated to normal levels during the first 20 to 30 hours of incubation in the presence of DFO. Furthermore, p33cdk2 was activated as an H1 histone kinase. As active p33cdk2 primarily represents complexes of the p33 protein with cyclin E or cyclin A, the effects of DFO on these cyclins were examined. Although the induction of synthesis and early accumulation of cyclin E and cyclin E-associated kinase activity appeared normal, the appearance of cyclin A and cyclin A-associated kinase activity were inhibited by DFO. However, the production of cyclin A mRNA appeared to be normal in the presence of DFO. A major effect of DFO in blocking cell cycle progression may be mediated through inhibition of the appearance of cyclin A protein and, therefore, a major component of p33cdk2 activity. The results also indicate that the p33cdk2/cyclin E activity produced in the presence of DFO was not sufficient for completion of the G1 phase of the cell cycle.

Original languageEnglish
Pages (from-to)2268-2280
Number of pages13
JournalBlood
Volume86
Issue number6
Publication statusPublished - Sep 15 1995

Fingerprint

Cyclin-Dependent Kinase 2
Cyclin A
Deferoxamine
T-cells
Cell Cycle
Iron
Cells
T-Lymphocytes
Cyclin E
G1 Phase
Phosphotransferases
CDC2 Protein Kinase
Iron Chelating Agents
Proteins
Cyclins
Interleukins
Transcription
Chelating Agents
Cell Cycle Checkpoints
Genes

ASJC Scopus subject areas

  • Hematology

Cite this

Effects of iron-depletion on cell cycle progression in normal human T lymphocytes : Selective inhibition of the appearance of the cyclin A-associated component of the p33cdk2 kinase. / Lucas, Joseph J.; Szepesi, Agota; Domenico, Joanne; Takase, Kozo; Tordai, A.; Terada, Naohiro; Gelfand, Erwin W.

In: Blood, Vol. 86, No. 6, 15.09.1995, p. 2268-2280.

Research output: Contribution to journalArticle

Lucas, Joseph J. ; Szepesi, Agota ; Domenico, Joanne ; Takase, Kozo ; Tordai, A. ; Terada, Naohiro ; Gelfand, Erwin W. / Effects of iron-depletion on cell cycle progression in normal human T lymphocytes : Selective inhibition of the appearance of the cyclin A-associated component of the p33cdk2 kinase. In: Blood. 1995 ; Vol. 86, No. 6. pp. 2268-2280.
@article{4bd87cecc5784082ad1e7104fe23fed8,
title = "Effects of iron-depletion on cell cycle progression in normal human T lymphocytes: Selective inhibition of the appearance of the cyclin A-associated component of the p33cdk2 kinase",
abstract = "Iron removal by the chelating-agent deferoxamine (DFO) arrests cell cycle progression of activated human T cells in late G1 phase, before the G1/S border. The effects of the drug on molecules that regulate progression through the cell cycle were defined. DFO (10 μmol/L) inhibited induction of transcription of the cdc2 gene, but had no effect on accumulation of cdk2, cdk4, or interleukin (IL)-Z transcripts. No detectable p34cdc2 protein accumulated, but synthesis of the p33cdk2 protein was begun. It accumulated to normal levels during the first 20 to 30 hours of incubation in the presence of DFO. Furthermore, p33cdk2 was activated as an H1 histone kinase. As active p33cdk2 primarily represents complexes of the p33 protein with cyclin E or cyclin A, the effects of DFO on these cyclins were examined. Although the induction of synthesis and early accumulation of cyclin E and cyclin E-associated kinase activity appeared normal, the appearance of cyclin A and cyclin A-associated kinase activity were inhibited by DFO. However, the production of cyclin A mRNA appeared to be normal in the presence of DFO. A major effect of DFO in blocking cell cycle progression may be mediated through inhibition of the appearance of cyclin A protein and, therefore, a major component of p33cdk2 activity. The results also indicate that the p33cdk2/cyclin E activity produced in the presence of DFO was not sufficient for completion of the G1 phase of the cell cycle.",
author = "Lucas, {Joseph J.} and Agota Szepesi and Joanne Domenico and Kozo Takase and A. Tordai and Naohiro Terada and Gelfand, {Erwin W.}",
year = "1995",
month = "9",
day = "15",
language = "English",
volume = "86",
pages = "2268--2280",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "6",

}

TY - JOUR

T1 - Effects of iron-depletion on cell cycle progression in normal human T lymphocytes

T2 - Selective inhibition of the appearance of the cyclin A-associated component of the p33cdk2 kinase

AU - Lucas, Joseph J.

AU - Szepesi, Agota

AU - Domenico, Joanne

AU - Takase, Kozo

AU - Tordai, A.

AU - Terada, Naohiro

AU - Gelfand, Erwin W.

PY - 1995/9/15

Y1 - 1995/9/15

N2 - Iron removal by the chelating-agent deferoxamine (DFO) arrests cell cycle progression of activated human T cells in late G1 phase, before the G1/S border. The effects of the drug on molecules that regulate progression through the cell cycle were defined. DFO (10 μmol/L) inhibited induction of transcription of the cdc2 gene, but had no effect on accumulation of cdk2, cdk4, or interleukin (IL)-Z transcripts. No detectable p34cdc2 protein accumulated, but synthesis of the p33cdk2 protein was begun. It accumulated to normal levels during the first 20 to 30 hours of incubation in the presence of DFO. Furthermore, p33cdk2 was activated as an H1 histone kinase. As active p33cdk2 primarily represents complexes of the p33 protein with cyclin E or cyclin A, the effects of DFO on these cyclins were examined. Although the induction of synthesis and early accumulation of cyclin E and cyclin E-associated kinase activity appeared normal, the appearance of cyclin A and cyclin A-associated kinase activity were inhibited by DFO. However, the production of cyclin A mRNA appeared to be normal in the presence of DFO. A major effect of DFO in blocking cell cycle progression may be mediated through inhibition of the appearance of cyclin A protein and, therefore, a major component of p33cdk2 activity. The results also indicate that the p33cdk2/cyclin E activity produced in the presence of DFO was not sufficient for completion of the G1 phase of the cell cycle.

AB - Iron removal by the chelating-agent deferoxamine (DFO) arrests cell cycle progression of activated human T cells in late G1 phase, before the G1/S border. The effects of the drug on molecules that regulate progression through the cell cycle were defined. DFO (10 μmol/L) inhibited induction of transcription of the cdc2 gene, but had no effect on accumulation of cdk2, cdk4, or interleukin (IL)-Z transcripts. No detectable p34cdc2 protein accumulated, but synthesis of the p33cdk2 protein was begun. It accumulated to normal levels during the first 20 to 30 hours of incubation in the presence of DFO. Furthermore, p33cdk2 was activated as an H1 histone kinase. As active p33cdk2 primarily represents complexes of the p33 protein with cyclin E or cyclin A, the effects of DFO on these cyclins were examined. Although the induction of synthesis and early accumulation of cyclin E and cyclin E-associated kinase activity appeared normal, the appearance of cyclin A and cyclin A-associated kinase activity were inhibited by DFO. However, the production of cyclin A mRNA appeared to be normal in the presence of DFO. A major effect of DFO in blocking cell cycle progression may be mediated through inhibition of the appearance of cyclin A protein and, therefore, a major component of p33cdk2 activity. The results also indicate that the p33cdk2/cyclin E activity produced in the presence of DFO was not sufficient for completion of the G1 phase of the cell cycle.

UR - http://www.scopus.com/inward/record.url?scp=0029087637&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029087637&partnerID=8YFLogxK

M3 - Article

C2 - 7662974

AN - SCOPUS:0029087637

VL - 86

SP - 2268

EP - 2280

JO - Blood

JF - Blood

SN - 0006-4971

IS - 6

ER -