B-myc inhibits neoplastic transformation and transcriptional activation by c-myc - PubMed (original) (raw)
B-myc inhibits neoplastic transformation and transcriptional activation by c-myc
L M Resar et al. Mol Cell Biol. 1993 Feb.
Abstract
B-myc is a recently described myc gene whose product has not been functionally characterized. The predicted product of B-myc is a 168-amino-acid protein with extensive homology to the c-Myc amino-terminal region, previously shown to contain a transcriptional activation domain. We hypothesized that B-Myc might also function in transcriptional regulation, although its role in regulating gene expression is predicted to be unique, because B-Myc lacks the specific DNA-binding motif found in other Myc proteins. To determine whether B-Myc could interact with the transcriptional machinery, we studied the transcriptional activation properties of a chimeric protein containing B-Myc sequences fused to the DNA-binding domain of the yeast transcriptional activator GAL4 (GAL4-B-Myc). We found that GAL4-B-Myc strongly activated expression of a GAL4-regulated reporter gene in mammalian cells. In addition, full-length B-Myc was able to inhibit or squelch reporter gene activation by a GAL4 chimeric protein containing the c-Myc transcriptional activation domain. We also observed that B-Myc dramatically inhibited the neoplastic cotransforming activity of c-Myc and activated Ras in rat embryo cells. Because B-Myc inhibits both neoplastic transformation and transcriptional activation by c-Myc, we suggest that the transforming activity of c-Myc is related to its ability to regulate transcription. Whether B-Myc functions biologically to squelch transcription and/or to regulate transcription through a specific DNA-binding protein remains unestablished.
Similar articles
- Activation domains of L-Myc and c-Myc determine their transforming potencies in rat embryo cells.
Barrett J, Birrer MJ, Kato GJ, Dosaka-Akita H, Dang CV. Barrett J, et al. Mol Cell Biol. 1992 Jul;12(7):3130-7. doi: 10.1128/mcb.12.7.3130-3137.1992. Mol Cell Biol. 1992. PMID: 1620120 Free PMC article. - Intracellular leucine zipper interactions suggest c-Myc hetero-oligomerization.
Dang CV, Barrett J, Villa-Garcia M, Resar LM, Kato GJ, Fearon ER. Dang CV, et al. Mol Cell Biol. 1991 Feb;11(2):954-62. doi: 10.1128/mcb.11.2.954-962.1991. Mol Cell Biol. 1991. PMID: 1990293 Free PMC article. - An essential domain of the c-myc protein interacts with a nuclear factor that is also required for E1A-mediated transformation.
Brough DE, Hofmann TJ, Ellwood KB, Townley RA, Cole MD. Brough DE, et al. Mol Cell Biol. 1995 Mar;15(3):1536-44. doi: 10.1128/MCB.15.3.1536. Mol Cell Biol. 1995. PMID: 7862146 Free PMC article. - Mechanism of transcriptional activation by the Myc oncoproteins.
Cowling VH, Cole MD. Cowling VH, et al. Semin Cancer Biol. 2006 Aug;16(4):242-52. doi: 10.1016/j.semcancer.2006.08.001. Epub 2006 Aug 4. Semin Cancer Biol. 2006. PMID: 16935524 Review. - MYC cofactors: molecular switches controlling diverse biological outcomes.
Hann SR. Hann SR. Cold Spring Harb Perspect Med. 2014 Jun 17;4(9):a014399. doi: 10.1101/cshperspect.a014399. Cold Spring Harb Perspect Med. 2014. PMID: 24939054 Free PMC article. Review.
Cited by
- Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice.
Thakur A, Bollig A, Wu J, Liao DJ. Thakur A, et al. Mol Cancer. 2008 Jan 24;7:11. doi: 10.1186/1476-4598-7-11. Mol Cancer. 2008. PMID: 18218118 Free PMC article. - Structure of pp32, an acidic nuclear protein which inhibits oncogene-induced formation of transformed foci.
Chen TH, Brody JR, Romantsev FE, Yu JG, Kayler AE, Voneiff E, Kuhajda FP, Pasternack GR. Chen TH, et al. Mol Biol Cell. 1996 Dec;7(12):2045-56. doi: 10.1091/mbc.7.12.2045. Mol Biol Cell. 1996. PMID: 8970164 Free PMC article. - Impairment of liver regeneration by the histone deacetylase inhibitor valproic acid in mice.
Ke Q, Yang RN, Ye F, Wang YJ, Wu Q, Li L, Bu H. Ke Q, et al. J Zhejiang Univ Sci B. 2012 Sep;13(9):695-706. doi: 10.1631/jzus.B1100362. J Zhejiang Univ Sci B. 2012. PMID: 22949360 Free PMC article. - MB0 and MBI Are Independent and Distinct Transactivation Domains in MYC that Are Essential for Transformation.
Zhang Q, West-Osterfield K, Spears E, Li Z, Panaccione A, Hann SR. Zhang Q, et al. Genes (Basel). 2017 May 6;8(5):134. doi: 10.3390/genes8050134. Genes (Basel). 2017. PMID: 28481271 Free PMC article. - Ribosome stalling during c-myc translation presents actionable cancer cell vulnerability.
Khaket TP, Rimal S, Wang X, Bhurtel S, Wu YC, Lu B. Khaket TP, et al. PNAS Nexus. 2024 Aug 13;3(8):pgae321. doi: 10.1093/pnasnexus/pgae321. eCollection 2024 Aug. PNAS Nexus. 2024. PMID: 39161732 Free PMC article.
References
- Mol Cell Biol. 1985 Feb;5(2):410-3 - PubMed
- J Virol. 1982 Jun;42(3):773-9 - PubMed
- Mol Cell Biol. 1987 May;7(5):1697-709 - PubMed
- EMBO J. 1987 Aug;6(8):2365-71 - PubMed
- Mol Cell Biol. 1988 Jan;8(1):186-95 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources