Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle

Research output: Contribution to journalJournal articlepeer-review

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Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle. / Skouv, J.; Jensen, P O; Forchhammer, J; Larsen, J K; Lund, L R.

In: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, Vol. 5, No. 3, 03.1994, p. 329-40.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Skouv, J, Jensen, PO, Forchhammer, J, Larsen, JK & Lund, LR 1994, 'Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle', Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, vol. 5, no. 3, pp. 329-40.

APA

Skouv, J., Jensen, P. O., Forchhammer, J., Larsen, J. K., & Lund, L. R. (1994). Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 5(3), 329-40.

Vancouver

Skouv J, Jensen PO, Forchhammer J, Larsen JK, Lund LR. Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1994 Mar;5(3):329-40.

Author

Skouv, J. ; Jensen, P O ; Forchhammer, J ; Larsen, J K ; Lund, L R. / Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle. In: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1994 ; Vol. 5, No. 3. pp. 329-40.

Bibtex

@article{66002f095b614215b73a00e73c75c432,
title = "Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle",
abstract = "Activation of the protein kinase C signaling pathway by tumor-promoting phorbol esters, such as 4 beta-phorbol 12-myristate 13-acetate (PMA), induced a decrease in the level of p53 mRNA in several serum-starved human cell lines. Also, the tumor-promoting phosphatase inhibitor okadaic acid induced a decrease in the p53 mRNA level in the cell lines. Normal diploid as well as various tumor cell lines were tested. Two tumor cell lines, HeLa and A549, both containing the wild-type p53 gene, but very different levels of p53 protein, were studied in detail. In both cell lines, the level of p53 mRNA was minimal after 9 h of exposure to PMA. After approximately 120 h, the p53 mRNA level was similar to the pretreatment level. PMA induced a similar transient decrease in the level of p53 protein in the A549 cell line. The decrease in the p53 mRNA level could not be explained by changes in the transcriptional rate or the p53 mRNA stability. The protein synthesis inhibitor cycloheximide completely abolished the PMA-induced down-modulation of the p53 mRNA, suggesting that a short-lived protein was involved in the down-modulation. Flow cytometric cell cycle analysis showed that the phorbol ester treatment induced a block in the late G1 phase. The blockage was transient, and its duration correlated with the level of p53 protein in the two cell lines. We propose that the protein kinase C-catalyzed phosphorylation of p53 may be a key event in the down-modulation of p53 expression as well as in the induced blockage of the cell cycle.",
keywords = "Cell Cycle, Cycloheximide, Down-Regulation, Ethers, Cyclic, Half-Life, Humans, Okadaic Acid, Protein Kinase C, RNA, Messenger, Tetradecanoylphorbol Acetate, Time Factors, Transcription, Genetic, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Journal Article, Research Support, Non-U.S. Gov't",
author = "J. Skouv and Jensen, {P O} and J Forchhammer and Larsen, {J K} and Lund, {L R}",
year = "1994",
month = mar,
language = "English",
volume = "5",
pages = "329--40",
journal = "Cell Growth and Differentiation",
issn = "1044-9523",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle

AU - Skouv, J.

AU - Jensen, P O

AU - Forchhammer, J

AU - Larsen, J K

AU - Lund, L R

PY - 1994/3

Y1 - 1994/3

N2 - Activation of the protein kinase C signaling pathway by tumor-promoting phorbol esters, such as 4 beta-phorbol 12-myristate 13-acetate (PMA), induced a decrease in the level of p53 mRNA in several serum-starved human cell lines. Also, the tumor-promoting phosphatase inhibitor okadaic acid induced a decrease in the p53 mRNA level in the cell lines. Normal diploid as well as various tumor cell lines were tested. Two tumor cell lines, HeLa and A549, both containing the wild-type p53 gene, but very different levels of p53 protein, were studied in detail. In both cell lines, the level of p53 mRNA was minimal after 9 h of exposure to PMA. After approximately 120 h, the p53 mRNA level was similar to the pretreatment level. PMA induced a similar transient decrease in the level of p53 protein in the A549 cell line. The decrease in the p53 mRNA level could not be explained by changes in the transcriptional rate or the p53 mRNA stability. The protein synthesis inhibitor cycloheximide completely abolished the PMA-induced down-modulation of the p53 mRNA, suggesting that a short-lived protein was involved in the down-modulation. Flow cytometric cell cycle analysis showed that the phorbol ester treatment induced a block in the late G1 phase. The blockage was transient, and its duration correlated with the level of p53 protein in the two cell lines. We propose that the protein kinase C-catalyzed phosphorylation of p53 may be a key event in the down-modulation of p53 expression as well as in the induced blockage of the cell cycle.

AB - Activation of the protein kinase C signaling pathway by tumor-promoting phorbol esters, such as 4 beta-phorbol 12-myristate 13-acetate (PMA), induced a decrease in the level of p53 mRNA in several serum-starved human cell lines. Also, the tumor-promoting phosphatase inhibitor okadaic acid induced a decrease in the p53 mRNA level in the cell lines. Normal diploid as well as various tumor cell lines were tested. Two tumor cell lines, HeLa and A549, both containing the wild-type p53 gene, but very different levels of p53 protein, were studied in detail. In both cell lines, the level of p53 mRNA was minimal after 9 h of exposure to PMA. After approximately 120 h, the p53 mRNA level was similar to the pretreatment level. PMA induced a similar transient decrease in the level of p53 protein in the A549 cell line. The decrease in the p53 mRNA level could not be explained by changes in the transcriptional rate or the p53 mRNA stability. The protein synthesis inhibitor cycloheximide completely abolished the PMA-induced down-modulation of the p53 mRNA, suggesting that a short-lived protein was involved in the down-modulation. Flow cytometric cell cycle analysis showed that the phorbol ester treatment induced a block in the late G1 phase. The blockage was transient, and its duration correlated with the level of p53 protein in the two cell lines. We propose that the protein kinase C-catalyzed phosphorylation of p53 may be a key event in the down-modulation of p53 expression as well as in the induced blockage of the cell cycle.

KW - Cell Cycle

KW - Cycloheximide

KW - Down-Regulation

KW - Ethers, Cyclic

KW - Half-Life

KW - Humans

KW - Okadaic Acid

KW - Protein Kinase C

KW - RNA, Messenger

KW - Tetradecanoylphorbol Acetate

KW - Time Factors

KW - Transcription, Genetic

KW - Tumor Cells, Cultured

KW - Tumor Suppressor Protein p53

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Journal article

C2 - 8018565

VL - 5

SP - 329

EP - 340

JO - Cell Growth and Differentiation

JF - Cell Growth and Differentiation

SN - 1044-9523

IS - 3

ER -

ID: 181873979