An amino-terminal c-myc domain required for neoplastic transformation activates transcription - PubMed (original) (raw)
An amino-terminal c-myc domain required for neoplastic transformation activates transcription
G J Kato et al. Mol Cell Biol. 1990 Nov.
Abstract
The product of the c-myc proto-oncogene is a nuclear phosphoprotein whose normal cellular function has not yet been defined. c-Myc has a number of biochemical properties, however, that suggest that it may function as a potential regulator of gene transcription. Specifically, it is a nuclear DNA-binding protein with a short half-life, a high proline content, segments that are rich in glutamine and acidic residues, and a carboxyl-terminal oligomerization domain containing the leucine zipper and helix-loop-helix motifs that serve as oligomerization domains in known regulators of transcription, such as C/EBP, Jun, Fos, GCN4, MyoD, E12, and E47. In an effort to establish that c-Myc might regulate transcription in vivo, we sought to determine whether regions of the c-Myc protein could activate transcription in an in vitro system. We report here that fusion proteins in which segments of human c-Myc are linked to the DNA-binding domain of the yeast transcriptional activator GAL4 can activate transcription from a reporter gene linked to GAL4-binding sites. Three independent activation regions are located between amino acids 1 and 143, a region that has been shown to be required for neoplastic transformation of primary rat embryo cells in cooperation with a mutated ras gene. These results demonstrate that domains of the c-Myc protein can function to regulate transcription in a model system and suggest that alterations of Myc transcriptional regulatory function may lead to neoplastic transformation.
Similar articles
- 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. - 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. - B-myc inhibits neoplastic transformation and transcriptional activation by c-myc.
Resar LM, Dolde C, Barrett JF, Dang CV. Resar LM, et al. Mol Cell Biol. 1993 Feb;13(2):1130-6. doi: 10.1128/mcb.13.2.1130-1136.1993. Mol Cell Biol. 1993. PMID: 8423780 Free PMC article. - Differentiation primary response genes and proto-oncogenes as positive and negative regulators of terminal hematopoietic cell differentiation.
Liebermann DA, Hoffman B. Liebermann DA, et al. Stem Cells. 1994 Jul;12(4):352-69. doi: 10.1002/stem.5530120402. Stem Cells. 1994. PMID: 7951003 Review. - Target genes and cellular regulators of the Myc transcription complex.
Peters MA, Taparowsky EJ. Peters MA, et al. Crit Rev Eukaryot Gene Expr. 1998;8(3-4):277-96. doi: 10.1615/critreveukargeneexpr.v8.i3-4.30. Crit Rev Eukaryot Gene Expr. 1998. PMID: 9807697 Review.
Cited by
- Missense Mutations in Myc Box I Influence Nucleocytoplasmic Transport to Promote Leukemogenesis.
Arthur NBJ, Christensen KA, Mannino K, Ruzinova MB, Kumar A, Gruszczynska A, Day RB, Erdmann-Gilmore P, Mi Y, Sprung R, York CR, Townsend RR, Spencer DH, Sykes SM, Ferraro F. Arthur NBJ, et al. Clin Cancer Res. 2024 Aug 15;30(16):3622-3639. doi: 10.1158/1078-0432.CCR-24-0926. Clin Cancer Res. 2024. PMID: 38848040 - Isoform-Directed Control of c-Myc Functions: Understanding the Balance from Proliferation to Growth Arrest.
Kubickova A, De Sanctis JB, Hajduch M. Kubickova A, et al. Int J Mol Sci. 2023 Dec 15;24(24):17524. doi: 10.3390/ijms242417524. Int J Mol Sci. 2023. PMID: 38139353 Free PMC article. Review. - MYC function and regulation in physiological perspective.
Jha RK, Kouzine F, Levens D. Jha RK, et al. Front Cell Dev Biol. 2023 Oct 24;11:1268275. doi: 10.3389/fcell.2023.1268275. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 37941901 Free PMC article. Review. - Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence.
Murali R, Balasubramaniam V, Srinivas S, Sundaram S, Venkatraman G, Warrier S, Dharmarajan A, Gandhirajan RK. Murali R, et al. Metabolites. 2023 Apr 15;13(4):560. doi: 10.3390/metabo13040560. Metabolites. 2023. PMID: 37110218 Free PMC article. Review. - Lipid Metabolic Reprogramming in Embryonal Neoplasms with MYCN Amplification.
Talapatra J, Reddy MM. Talapatra J, et al. Cancers (Basel). 2023 Apr 4;15(7):2144. doi: 10.3390/cancers15072144. Cancers (Basel). 2023. PMID: 37046804 Free PMC article. Review.
References
- EMBO J. 1990 Apr;9(4):1113-21 - PubMed
- Genes Dev. 1990 Feb;4(2):167-79 - PubMed
- Mol Cell Biol. 1990 Jun;10(6):2591-8 - PubMed
- Mol Cell Biol. 1990 Jun;10(6):2840-7 - PubMed
- Cell Growth Differ. 1990 Jul;1(7):339-43 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous