c-Myc Rabbit Polyclonal Antibody

Function

Myc is a family of regulator genes and proto-oncogenes that code for transcription factors. The Myc family consists of three related human genes: c-myc (MYC), l-myc (MYCL), and n-myc (MYCN). c-myc (also sometimes referred to as MYC) was the first gene to be discovered in this family, due to homology with the viral gene v-myc. In cancer, c-myc is often constitutively (persistently) expressed. This leads to the increased expression of many genes, some of which are involved in cell proliferation, contributing to the formation of cancer. A common human translocation involving c-myc is critical to the development of most cases of Burkitt lymphoma. Constitutive upregulation of Myc genes have also been observed in carcinoma of the cervix, colon, breast, lung and stomach. Myc is thus viewed as a promising target for anti-cancer drugs. Unfortunately, Myc possesses several features that render it undruggable such that any anti-cancer drugs for Myc dysregulation will require acting on the protein indirectly, i.e. targeting the mRNA for the protein rather than a small molecule that targets the protein itself. In the human genome, C-myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes through binding on enhancer box sequences (E-boxes). In addition to its role as a classical transcription factor, N-myc may recruit histone acetyltransferases (HATs). This allows it to regulate global chromatin structure via histone acetylation.

Background References

1. "A quantitative atlas of mitotic phosphorylation."Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008)

2. "Transactivation of gene expression by Myc is inhibited by mutation at the phosphorylation sites Thr-58 and Ser-62."Gupta S., Seth A., Davis R.J. Proc. Natl. Acad. Sci. U.S.A. 90:3216-3220(1993)

Post-translational Modification

Phosphorylated by PRKDC. Phosphorylation at Ser-329 by PIM2 leads to the stabilization of MYC (By similarity). Phosphorylation at Ser-62 by CDK2 prevents Ras-induced senescence. Phosphorylated at Ser-62 by DYRK2; this primes the protein for subsequent phosphorylation by GSK3B at Thr-58. Phosphorylation at Thr-58 and Ser-62 by GSK3 is required for ubiquitination and degradation by the proteasome.; Ubiquitinated by the SCF(FBXW7) complex when phosphorylated at Thr-58 and Ser-62, leading to its degradation by the proteasome. In the nucleoplasm, ubiquitination is counteracted by USP28, which interacts with isoform 1 of FBXW7 (FBW7alpha), leading to its deubiquitination and preventing degradation. In the nucleolus, however, ubiquitination is not counteracted by USP28 but by USP36, due to the lack of interaction between isoform 3 of FBXW7 (FBW7gamma) and USP28, explaining the selective MYC degradation in the nucleolus. Also polyubiquitinated by the DCX(TRUSS) complex. Ubiquitinated by TRIM6 in a phosphorylation-independent manner (By similarity).

Subcellular Location

Nucleus.

UNIPROT

SwissProt: P01106 Human

Synonyms