Transcriptional activation by Myc is under negative control by the transcription factor AP-2 - PubMed (original) (raw)

Transcriptional activation by Myc is under negative control by the transcription factor AP-2

S Gaubatz et al. EMBO J. 1995.

Abstract

The Myc protein binds to and transactivates the expression of genes via E-box elements containing a central CAC(G/A)TG sequence. The transcriptional activation function of Myc is required for its ability to induce cell cycle progression, cellular transformation and apoptosis. Here we show that transactivation by Myc is under negative control by the transcription factor AP-2. AP-2 inhibits transactivation by Myc via two distinct mechanisms. First, high affinity binding sites for AP-2 overlap Myc-response elements in two bona fide target genes of Myc, prothymosin-alpha and ornithine decarboxylase. On these sites, AP-2 competes for binding of either Myc/Max heterodimers or Max/Max homodimers. The second mechanism involves a specific interaction between C-terminal domains of AP-2 and the BR/HLH/LZ domain of Myc, but not Max or Mad. Binding of AP-2 to Myc does not preclude association of Myc with Max, but impairs DNA binding of the Myc/Max complex and inhibits transactivation by Myc even in the absence of an overlapping AP-2 binding site. Taken together, our data suggest that AP-2 acts as a negative regulator of transactivation by Myc.

PubMed Disclaimer

Cited by

Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis.
Zhao Y, Liu J, Liu S, Yang P, Liang Y, Ma J, Mao S, Sun C, Yang Y. Zhao Y, et al. Bioact Mater. 2023 Mar 9;26:249-263. doi: 10.1016/j.bioactmat.2023.03.002. eCollection 2023 Aug. Bioact Mater. 2023. PMID: 36936807 Free PMC article.
GRHL2 and AP2a coordinate early surface ectoderm lineage commitment during development.
Collier AE, Piekos SN, Liu A, Pattison JM, Felix F, Bailetti AA, Sedov E, Gaddam S, Zhen H, Oro AE. Collier AE, et al. iScience. 2023 Feb 3;26(3):106125. doi: 10.1016/j.isci.2023.106125. eCollection 2023 Mar 17. iScience. 2023. PMID: 36843855 Free PMC article.
Isotretinoin and Thalidomide Down-Regulate c-MYC Gene Expression and Modify Proteins Associated with Cancer in Hepatic Cells.
Ramírez-Flores PN, Barraza-Reyna PJ, Aguirre-Vázquez A, Camacho-Moll ME, Guerrero-Beltrán CE, Resendez-Pérez D, González-Villasana V, Garza-González JN, Silva-Ramírez B, Castorena-Torres F, Bermúdez de León M. Ramírez-Flores PN, et al. Molecules. 2021 Sep 22;26(19):5742. doi: 10.3390/molecules26195742. Molecules. 2021. PMID: 34641286 Free PMC article.
MYC dysfunction modulates stemness and tumorigenesis in breast cancer.
Liu Y, Zhu C, Tang L, Chen Q, Guan N, Xu K, Guan X. Liu Y, et al. Int J Biol Sci. 2021 Jan 1;17(1):178-187. doi: 10.7150/ijbs.51458. eCollection 2021. Int J Biol Sci. 2021. PMID: 33390842 Free PMC article.
The functions and mechanisms of prefoldin complex and prefoldin-subunits.
Liang J, Xia L, Oyang L, Lin J, Tan S, Yi P, Han Y, Luo X, Wang H, Tang L, Pan Q, Tian Y, Rao S, Su M, Shi Y, Cao D, Zhou Y, Liao Q. Liang J, et al. Cell Biosci. 2020 Jul 20;10:87. doi: 10.1186/s13578-020-00446-8. eCollection 2020. Cell Biosci. 2020. PMID: 32699605 Free PMC article. Review.

References

1. Mol Cell Biol. 1993 Jul;13(7):4174-85 - PubMed
1. Blood. 1993 Aug 15;82(4):1127-32 - PubMed
1. Mol Cell Biol. 1993 Sep;13(9):5216-24 - PubMed
1. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7804-8 - PubMed
1. Oncogene. 1993 Oct;8(10):2821-6 - PubMed

Transcriptional activation by Myc is under negative control by the transcription factor AP-2 - PubMed (original) (raw)