Anti-Phospho-c-Myc: Rabbit c-Myc, Phospho-Thr58/Ser62 Antibody

BACKGROUND c-Myc belongs to the family of Myc proteins that includes B-Myc, L-Myc, N-Myc, and s-Myc; however, only c-Myc, L-Myc, and N-Myc have neoplastic potential. c-Myc is widely expressed. It is crucial for cell proliferation, differentiation and apoptosis in normal and neoplastic settings. It also regulates the expression of metabolic enzymes.  Following mitogenic stimulation of normal quiescent cells, c-Myc is rapidly induced and remains elevated, suggesting that it is required for continuous cell growth. Associated with its ability to drive proliferation is an equally potent ability to drive apoptosis. However, this feature is latent and only revealed in normal cells if c-Myc expression is uncoupled from survival signals mediated by cytokine and adhesion receptors.¹

 

c-Myc is a transcription factor which activates and represses different target genes. Its actions to induce and repress genes are modulated by interactions with other regulatory proteins. The C-terminal domain (CTD) of c-Myc mediates DNA binding to physiological target genes through a heterodimer complex with basic region/helix - loop - helix/`leucine zipper' (b/HLH/Z) protein Max. Another small bHLHZip protein, Mad, can bind Max too. Mad has been shown to abrogate the positive transcriptional activity of Myc. Mad:Max complexes are detected during differentiation and appear to replace the Myc:Max complexes present in proliferating cell populations. Because Myc and Mad proteins are expressed in response to diverse signaling pathways, the Myc/Max/Mad network can be viewed as a functional module which acts to convert environmental signals into specific gene-regulatory programs.² The N-terminal domain (NTD) of c-Myc includes the transcription activation domain (TAD). Two short segments in the NTD termed Myc boxes 1 and 2 (MB1 and MB2) are conserved in all Myc family proteins and are crucial for all biological activities. The NTD also mediates transcriptional repression.  New CTD-interacting proteins reinforce the role of this region in mediating specific DNA binding and suggest novel levels at which DNA binding is regulated. New NTD-binding proteins suggest links to the transcriptional regulatory machinery. Moreover, it was shown that that the NH2-terminal phosphorylation sites Thr-58 and Ser-62 are required for high levels of transactivation of gene expression by Myc.  MAP kinases catalyized the phosphorylation of these sites.³

 

The quantity of c-Myc is carefully controlled by many mechanisms. It can be functionally deregulated by both genetic and epigenetic mechanisms, for example, by chromosomal translocation or by constitutive expression due to activation of upstream-acting growth factor receptors, respectively. Many studies have documented c-Myc overexpression and mutations in cancer. Recent studies indicated activation of c-Myc gene expression is central to signal transduction through the adenomatous polyposis coli (APC) tumor suppressor protein which negatively regulates beta-catenin. beta-Catenin is a coactivator for the transcription factor TCF, which is able to directly activate c-myc expression, so that when APC is inactivated, activation of beta-catenin results. The activities of human transforming proteins BCR-ABL and TEL-PDGFR and proto-oncogenes c-Src and Wnt have been shown to depend on the c-myc gene ezpression.⁴
 

REFERENCES  

1. Lüscher, B. & Larsson, L.G.:Oncogene 18:2955-66, 1999
2. Sakamuro, D. & Prendergast, G.C.: Oncogene 18:2942-54, 1999
3. Gupta, S. et al: Proc. Natl. Acad. Sci. USA 90:3216-20, 1993
4. Dang, C.V.: Mol. Cell. Biol. 19:1-11, 1999