Ras enhances Myc protein stability

Rosalie Sears, Gustavo Leone, James DeGregori, Joseph R. Nevins

Research output: Contribution to journalArticle

320 Citations (Scopus)

Abstract

Various experiments have demonstrated a collaborative action of Myc and Ras, both in normal cell growth control as well as during oncogenesis. We now show that Ras enhances the accumulation of Myc activity by stabilizing the Myc protein. Whereas Myc has a very short half-life when produced in the absence of mitogenic signals, due to degradation by the 26S proteasome, the half-life of Myc increases markedly in growth-stimulated cells. This stabilization is dependent on the Ras/Raf/MAPK pathway and is not augmented by proteasome inhibition, suggesting that Ras inhibits the proteasome- dependent degradation of Myc. We propose that one aspect of Myc-Ras collaboration is an ability of Ras to enhance the accumulation of transcriptionally active Myc protein.

Original languageEnglish (US)
Pages (from-to)169-179
Number of pages11
JournalMolecular Cell
Volume3
Issue number2
DOIs
StatePublished - Feb 1999
Externally publishedYes

Fingerprint

Protein Stability
Proteasome Endopeptidase Complex
Half-Life
Growth
Carcinogenesis
Proteins
ATP dependent 26S protease

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Sears, R., Leone, G., DeGregori, J., & Nevins, J. R. (1999). Ras enhances Myc protein stability. Molecular Cell, 3(2), 169-179. https://doi.org/10.1016/S1097-2765(00)80308-1

Ras enhances Myc protein stability. / Sears, Rosalie; Leone, Gustavo; DeGregori, James; Nevins, Joseph R.

In: Molecular Cell, Vol. 3, No. 2, 02.1999, p. 169-179.

Research output: Contribution to journalArticle

Sears, R, Leone, G, DeGregori, J & Nevins, JR 1999, 'Ras enhances Myc protein stability', Molecular Cell, vol. 3, no. 2, pp. 169-179. https://doi.org/10.1016/S1097-2765(00)80308-1
Sears, Rosalie ; Leone, Gustavo ; DeGregori, James ; Nevins, Joseph R. / Ras enhances Myc protein stability. In: Molecular Cell. 1999 ; Vol. 3, No. 2. pp. 169-179.
@article{02b330d37752453899e01966e2e778a0,
title = "Ras enhances Myc protein stability",
abstract = "Various experiments have demonstrated a collaborative action of Myc and Ras, both in normal cell growth control as well as during oncogenesis. We now show that Ras enhances the accumulation of Myc activity by stabilizing the Myc protein. Whereas Myc has a very short half-life when produced in the absence of mitogenic signals, due to degradation by the 26S proteasome, the half-life of Myc increases markedly in growth-stimulated cells. This stabilization is dependent on the Ras/Raf/MAPK pathway and is not augmented by proteasome inhibition, suggesting that Ras inhibits the proteasome- dependent degradation of Myc. We propose that one aspect of Myc-Ras collaboration is an ability of Ras to enhance the accumulation of transcriptionally active Myc protein.",
author = "Rosalie Sears and Gustavo Leone and James DeGregori and Nevins, {Joseph R.}",
year = "1999",
month = "2",
doi = "10.1016/S1097-2765(00)80308-1",
language = "English (US)",
volume = "3",
pages = "169--179",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Ras enhances Myc protein stability

AU - Sears, Rosalie

AU - Leone, Gustavo

AU - DeGregori, James

AU - Nevins, Joseph R.

PY - 1999/2

Y1 - 1999/2

N2 - Various experiments have demonstrated a collaborative action of Myc and Ras, both in normal cell growth control as well as during oncogenesis. We now show that Ras enhances the accumulation of Myc activity by stabilizing the Myc protein. Whereas Myc has a very short half-life when produced in the absence of mitogenic signals, due to degradation by the 26S proteasome, the half-life of Myc increases markedly in growth-stimulated cells. This stabilization is dependent on the Ras/Raf/MAPK pathway and is not augmented by proteasome inhibition, suggesting that Ras inhibits the proteasome- dependent degradation of Myc. We propose that one aspect of Myc-Ras collaboration is an ability of Ras to enhance the accumulation of transcriptionally active Myc protein.

AB - Various experiments have demonstrated a collaborative action of Myc and Ras, both in normal cell growth control as well as during oncogenesis. We now show that Ras enhances the accumulation of Myc activity by stabilizing the Myc protein. Whereas Myc has a very short half-life when produced in the absence of mitogenic signals, due to degradation by the 26S proteasome, the half-life of Myc increases markedly in growth-stimulated cells. This stabilization is dependent on the Ras/Raf/MAPK pathway and is not augmented by proteasome inhibition, suggesting that Ras inhibits the proteasome- dependent degradation of Myc. We propose that one aspect of Myc-Ras collaboration is an ability of Ras to enhance the accumulation of transcriptionally active Myc protein.

UR - http://www.scopus.com/inward/record.url?scp=0033082892&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033082892&partnerID=8YFLogxK

U2 - 10.1016/S1097-2765(00)80308-1

DO - 10.1016/S1097-2765(00)80308-1

M3 - Article

VL - 3

SP - 169

EP - 179

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 2

ER -