JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Add like
Add dislike
Add to saved papers

c-Myc inhibits Ras-mediated differentiation of pheochromocytoma cells by blocking c-Jun up-regulation.

Although mutant Ras proteins were originally described as transforming oncoproteins, they induce growth arrest, senescence, and/or differentiation in many cell types. c-Myc is an oncogenic transcription factor that cooperates with Ras in cellular transformation and oncogenesis. However, the Myc-Ras relationship in cellular differentiation is largely unknown. Here, we have analyzed the effects of c-Myc on PC12-derived cells (UR61 cell line), harboring an inducible N-Ras oncogene. In these cells, Ras activation induces neuronal-like differentiation by a process involving c-Jun activation. We found that c-Myc inhibited Ras-mediated differentiation by a mechanism that involves the blockade of c-Jun induction in response to Ras signal. Accordingly, ectopically expressed c-Jun could bypass c-Myc impediment of Ras-induced differentiation and activator protein 1 activation. Interestingly, it did not rescue the proliferative arrest elicited by Ras and did not enhance the differentiation-associated apoptosis. The blockade of Ras-mediated induction of c-Jun takes place at the level of c-Jun proximal promoter. Mutational analysis revealed that c-Myc regions involved in DNA binding and transactivation are required to block differentiation and c-Jun induction. c-Myc does not seem to require Miz-1 to inhibit differentiation and block c-Jun induction. Furthermore, Max is not required for c-Myc activity, as UR61 cells lack a functional Max gene. c-Myc-inhibitory effect on the Ras/c-Jun connection is not restricted to UR61 cells as it can occur in other cell types as K562 or HEK293. In conclusion, we describe a novel interplay between c-Myc and c-Jun that controls the ability of Ras to trigger the differentiation program of pheochromocytoma cells.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app