Induction of the nuclear proto-oncogene c-fos by the phorbol ester TPA and v-H-Ras.
(2008) In Molecules and Cells 26(5). p.462-467- Abstract
- TPA is known to cooperate with an activated Ras oncogene in the transformation of rodent fibroblasts, but the biochemical mechanisms responsible for this effect have not been established. In the present study we used c-fos promoter-luciferase constructs as reporters, in transient transfection assays, in NIH3T3 cells to assess the mechanism of this cooperation. We found a marked synergistic interaction between TPA and a transfected v-Ha-ras oncogene in the activation of c-fos promoter and SRE. SRE has binding sites for TCF and SRF. A dominant-negative Ras (ras-N17) inhibited the TPA-Ras synergy by blocking the PKC-MAPK-TCF pathway. Dominant-negative RhoA and Rac1 (but not Cdc42Hs) inhibited the TPA-Ras synergy by blocking the Ras-Rho-SRF... (More)
- TPA is known to cooperate with an activated Ras oncogene in the transformation of rodent fibroblasts, but the biochemical mechanisms responsible for this effect have not been established. In the present study we used c-fos promoter-luciferase constructs as reporters, in transient transfection assays, in NIH3T3 cells to assess the mechanism of this cooperation. We found a marked synergistic interaction between TPA and a transfected v-Ha-ras oncogene in the activation of c-fos promoter and SRE. SRE has binding sites for TCF and SRF. A dominant-negative Ras (ras-N17) inhibited the TPA-Ras synergy by blocking the PKC-MAPK-TCF pathway. Dominant-negative RhoA and Rac1 (but not Cdc42Hs) inhibited the TPA-Ras synergy by blocking the Ras-Rho-SRF signaling pathway. Constitutively active PKCalpha and PKCepsilon showed synergy with v-Ras. These results suggest that the activation of two distinct pathways such as Ras-Raf-ERK-TCF pathway and Rho-SRF pathway are responsible for the induction of c-fos by TPA and Ras in mitogenic signaling pathways. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3915785
- author
- Kazi, Julhash U. LU and Soh, Jae Won
- publishing date
- 2008-11-30
- type
- Contribution to journal
- publication status
- published
- in
- Molecules and Cells
- volume
- 26
- issue
- 5
- pages
- 462 - 467
- publisher
- Korean Society for Molecular and Cellular Biology
- external identifiers
-
- scopus:58049100970
- ISSN
- 1016-8478
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
- id
- 2fdec7b7-fc36-4976-9da6-ca66fed9c09d (old id 3915785)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18719353?dopt=AbstractPlus
- date added to LUP
- 2016-04-04 13:36:31
- date last changed
- 2022-01-30 00:35:11
@article{2fdec7b7-fc36-4976-9da6-ca66fed9c09d, abstract = {{TPA is known to cooperate with an activated Ras oncogene in the transformation of rodent fibroblasts, but the biochemical mechanisms responsible for this effect have not been established. In the present study we used c-fos promoter-luciferase constructs as reporters, in transient transfection assays, in NIH3T3 cells to assess the mechanism of this cooperation. We found a marked synergistic interaction between TPA and a transfected v-Ha-ras oncogene in the activation of c-fos promoter and SRE. SRE has binding sites for TCF and SRF. A dominant-negative Ras (ras-N17) inhibited the TPA-Ras synergy by blocking the PKC-MAPK-TCF pathway. Dominant-negative RhoA and Rac1 (but not Cdc42Hs) inhibited the TPA-Ras synergy by blocking the Ras-Rho-SRF signaling pathway. Constitutively active PKCalpha and PKCepsilon showed synergy with v-Ras. These results suggest that the activation of two distinct pathways such as Ras-Raf-ERK-TCF pathway and Rho-SRF pathway are responsible for the induction of c-fos by TPA and Ras in mitogenic signaling pathways.}}, author = {{Kazi, Julhash U. and Soh, Jae Won}}, issn = {{1016-8478}}, language = {{eng}}, month = {{11}}, number = {{5}}, pages = {{462--467}}, publisher = {{Korean Society for Molecular and Cellular Biology}}, series = {{Molecules and Cells}}, title = {{Induction of the nuclear proto-oncogene c-fos by the phorbol ester TPA and v-H-Ras.}}, url = {{https://lup.lub.lu.se/search/files/6161850/4250496.pdf}}, volume = {{26}}, year = {{2008}}, }