Negative regulation of Par-4 by oncogenic Ras is essential for cellular transformation

Shirley Guofang Qiu; Sumathi Krishnan; Nadia El-Guendy; Vivek M. Rangnekar

doi:10.1038/sj.onc.1203199

Negative regulation of Par-4 by oncogenic Ras is essential for cellular transformation

Shirley Guofang Qiu, Sumathi Krishnan, Nadia El-Guendy, Vivek M. Rangnekar

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

Oncogenic variants of the cellular Ras protein are often associated with different types of human cancers. However, the mechanisms by which oncogenic Ras induces transformation are not fully established. Expression of the transcriptional repressor Par-4 was down-regulated by oncogenic Ras via the Raf-MEK-ERK pathway. Restoration of Par-4 levels by abrogation of the Raf-MEK-ERK pathway with the MEK-inhibitor PD98059 or by ectopic Par-4, that acted to inhibit ERK expression and activation, was sufficient to suppress oncogenic Ras-induced transformation. These findings identify Par-4 as a novel target that has to be down-modulated by oncogenic Ras for successful transformation.

Original language	English
Pages (from-to)	7115-7123
Number of pages	9
Journal	Oncogene
Volume	18
Issue number	50
DOIs	https://doi.org/10.1038/sj.onc.1203199
State	Published - Nov 25 1999

Bibliographical note

Funding Information:
This work was supported by the NIH Grant R01 CA60872 (to VM Rangnekar).

Funding

This work was supported by the NIH Grant R01 CA60872 (to VM Rangnekar).

Funders	Funder number
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	R01CA060872

Keywords

ERK
Par-4
Pas
Transformation

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.onc.1203199

Cite this

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title = "Negative regulation of Par-4 by oncogenic Ras is essential for cellular transformation",

abstract = "Oncogenic variants of the cellular Ras protein are often associated with different types of human cancers. However, the mechanisms by which oncogenic Ras induces transformation are not fully established. Expression of the transcriptional repressor Par-4 was down-regulated by oncogenic Ras via the Raf-MEK-ERK pathway. Restoration of Par-4 levels by abrogation of the Raf-MEK-ERK pathway with the MEK-inhibitor PD98059 or by ectopic Par-4, that acted to inhibit ERK expression and activation, was sufficient to suppress oncogenic Ras-induced transformation. These findings identify Par-4 as a novel target that has to be down-modulated by oncogenic Ras for successful transformation.",

keywords = "ERK, Par-4, Pas, Transformation",

author = "Qiu, \{Shirley Guofang\} and Sumathi Krishnan and Nadia El-Guendy and Rangnekar, \{Vivek M.\}",

note = "Funding Information: This work was supported by the NIH Grant R01 CA60872 (to VM Rangnekar).",

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AU - Qiu, Shirley Guofang

AU - Krishnan, Sumathi

AU - El-Guendy, Nadia

AU - Rangnekar, Vivek M.

N1 - Funding Information: This work was supported by the NIH Grant R01 CA60872 (to VM Rangnekar).

PY - 1999/11/25

Y1 - 1999/11/25

N2 - Oncogenic variants of the cellular Ras protein are often associated with different types of human cancers. However, the mechanisms by which oncogenic Ras induces transformation are not fully established. Expression of the transcriptional repressor Par-4 was down-regulated by oncogenic Ras via the Raf-MEK-ERK pathway. Restoration of Par-4 levels by abrogation of the Raf-MEK-ERK pathway with the MEK-inhibitor PD98059 or by ectopic Par-4, that acted to inhibit ERK expression and activation, was sufficient to suppress oncogenic Ras-induced transformation. These findings identify Par-4 as a novel target that has to be down-modulated by oncogenic Ras for successful transformation.

AB - Oncogenic variants of the cellular Ras protein are often associated with different types of human cancers. However, the mechanisms by which oncogenic Ras induces transformation are not fully established. Expression of the transcriptional repressor Par-4 was down-regulated by oncogenic Ras via the Raf-MEK-ERK pathway. Restoration of Par-4 levels by abrogation of the Raf-MEK-ERK pathway with the MEK-inhibitor PD98059 or by ectopic Par-4, that acted to inhibit ERK expression and activation, was sufficient to suppress oncogenic Ras-induced transformation. These findings identify Par-4 as a novel target that has to be down-modulated by oncogenic Ras for successful transformation.

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KW - Par-4

KW - Pas

KW - Transformation

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Negative regulation of Par-4 by oncogenic Ras is essential for cellular transformation

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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