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Mage-A Cancer/Testis Antigens Inhibit p53 Function by Blocking Its Interaction with Chromatin

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Mage-A Cancer/Testis Antigens Inhibit p53 Function by Blocking Its Interaction with Chromatin. / Marcar, Lynnette; MacLaine, Nicola J.; Hupp, Ted R.; Meek, David W. (Lead / Corresponding author).

In: Cancer Research, Vol. 70, No. 24, 15.12.2010, p. 10362-10370.

Research output: Contribution to journalArticle

Harvard

Marcar, L, MacLaine, NJ, Hupp, TR & Meek, DW 2010, 'Mage-A Cancer/Testis Antigens Inhibit p53 Function by Blocking Its Interaction with Chromatin' Cancer Research, vol 70, no. 24, pp. 10362-10370., 10.1158/0008-5472.CAN-10-1341

APA

Marcar, L., MacLaine, N. J., Hupp, T. R., & Meek, D. W. (2010). Mage-A Cancer/Testis Antigens Inhibit p53 Function by Blocking Its Interaction with Chromatin. Cancer Research, 70(24), 10362-10370. 10.1158/0008-5472.CAN-10-1341

Vancouver

Marcar L, MacLaine NJ, Hupp TR, Meek DW. Mage-A Cancer/Testis Antigens Inhibit p53 Function by Blocking Its Interaction with Chromatin. Cancer Research. 2010 Dec 15;70(24):10362-10370. Available from: 10.1158/0008-5472.CAN-10-1341

Author

Marcar, Lynnette; MacLaine, Nicola J.; Hupp, Ted R.; Meek, David W. (Lead / Corresponding author) / Mage-A Cancer/Testis Antigens Inhibit p53 Function by Blocking Its Interaction with Chromatin.

In: Cancer Research, Vol. 70, No. 24, 15.12.2010, p. 10362-10370.

Research output: Contribution to journalArticle

Bibtex - Download

@article{3de9ab5ee7154a44837da55e86f09976,
title = "Mage-A Cancer/Testis Antigens Inhibit p53 Function by Blocking Its Interaction with Chromatin",
keywords = "IMMUNOCHEMICAL ANALYSIS, HUMAN TUMORS, EXPRESSION, CANCER, BINDING, GENES, CELLS, RECRUITMENT, SITE, ONCOPROTEIN",
author = "Lynnette Marcar and MacLaine, {Nicola J.} and Hupp, {Ted R.} and Meek, {David W.}",
year = "2010",
doi = "10.1158/0008-5472.CAN-10-1341",
volume = "70",
number = "24",
pages = "10362--10370",
journal = "Cancer Research",
issn = "0008-5472",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Mage-A Cancer/Testis Antigens Inhibit p53 Function by Blocking Its Interaction with Chromatin

A1 - Marcar,Lynnette

A1 - MacLaine,Nicola J.

A1 - Hupp,Ted R.

A1 - Meek,David W.

AU - Marcar,Lynnette

AU - MacLaine,Nicola J.

AU - Hupp,Ted R.

AU - Meek,David W.

PY - 2010/12/15

Y1 - 2010/12/15

N2 - <p>The p53 tumor suppressor plays a major protective role in tumor prevention by coordinating changes in gene expression that lead to the elimination of cancer cells. Mage-A proteins comprise a family of metastasis-associated transcriptional regulators that potently inhibit p53 function. Here, we show that Mage-A interacts with 3 distinct peptides each of which is located within the DNA binding surface of the core domain of p53 and encompasses amino acids that are critical for site-specific DNA binding. These data suggest that Mage-A may block the association of p53 with its cognate sites in chromatin. Consistent with this idea, silencing of Mage-A expression leads to upregulation of several p53-responsive genes in a p53-dependent manner and stimulates by several fold the interaction of p53 with the p21, MDM2, and PUMA promoters. Notably, these effects can occur in the absence of genotoxic stress, leading in a p53-dependent manner, to cell-cycle delay and increased cell death. These data reveal a novel mechanism by which Mage-A proteins may suppress the p53 transcriptional program during tumor development and highlight the p53/Mage-A interaction as a prospective therapeutic target. Cancer Res; 70( 24); 10362-70. (C)2010 AACR.</p>

AB - <p>The p53 tumor suppressor plays a major protective role in tumor prevention by coordinating changes in gene expression that lead to the elimination of cancer cells. Mage-A proteins comprise a family of metastasis-associated transcriptional regulators that potently inhibit p53 function. Here, we show that Mage-A interacts with 3 distinct peptides each of which is located within the DNA binding surface of the core domain of p53 and encompasses amino acids that are critical for site-specific DNA binding. These data suggest that Mage-A may block the association of p53 with its cognate sites in chromatin. Consistent with this idea, silencing of Mage-A expression leads to upregulation of several p53-responsive genes in a p53-dependent manner and stimulates by several fold the interaction of p53 with the p21, MDM2, and PUMA promoters. Notably, these effects can occur in the absence of genotoxic stress, leading in a p53-dependent manner, to cell-cycle delay and increased cell death. These data reveal a novel mechanism by which Mage-A proteins may suppress the p53 transcriptional program during tumor development and highlight the p53/Mage-A interaction as a prospective therapeutic target. Cancer Res; 70( 24); 10362-70. (C)2010 AACR.</p>

KW - IMMUNOCHEMICAL ANALYSIS

KW - HUMAN TUMORS

KW - EXPRESSION

KW - CANCER

KW - BINDING

KW - GENES

KW - CELLS

KW - RECRUITMENT

KW - SITE

KW - ONCOPROTEIN

UR - http://www.scopus.com/inward/record.url?scp=78650390294&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-10-1341

DO - 10.1158/0008-5472.CAN-10-1341

M1 - Article

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 24

VL - 70

SP - 10362

EP - 10370

ER -

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