We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The c-myc apoptotic response is not intrinsic to blocking terminal myeloid differentiation.
- Authors
D'Angelo, Santo; Liebermann, Dan; Hoffman, Barbara
- Abstract
It has previously been shown that deregulated c-myc blocks terminal myeloid differentiation and prematurely recruits both the Type I and II CD95/Fas apoptotic pathways, promoting an incompletely penetrant apoptotic response. In this work it is shown that deregulated expression of either mycER or mycER™ variants also blocked terminal myeloid differentiation but failed to induce the apoptotic response, demonstrating that c-myc can block differentiation independent of the apoptotic response. The failure of the mycER™ transgene to cause the apoptotic response is associated with reduced levels of RIP1 expression, increased Mcl-1 expression and activation of both NF-kB and Akt. In addition, deregulating expression of RIP1 in M1mycER™ cells restored the apoptotic response. Thus altering c-Myc or its downstream effectors can influence the balance between apoptosis and survival, and ultimately the oncogenic potential of the c-myc oncogene. This knowledge can be exploited to manipulate the downstream effectors, such as RIP1, to promote apoptosis and drive the death of cancer cells. J. Cell. Physiol. 216: 120–127, 2008. © 2008 Wiley-Liss, Inc.
- Subjects
APOPTOSIS; MYC oncogenes; TRANSGENES; ONCOGENES; CANCER cells; CELL death
- Publication
Journal of Cellular Physiology, 2008, Vol 216, Issue 1, p120
- ISSN
0021-9541
- Publication type
Article
- DOI
10.1002/jcp.21383