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Approximately 61,000 statements.
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Although it is not clear whether this is a direct effect, the CK2 sites within the acidic region might be relevant. This region lies within a PEST consensus sequence that has been shown to be involved in MYC protein degradation (18, 19). Thus it is interesting to speculate that CK2, which shows enhanced expression in many tumors (15, 20), affects cell proliferation at least in part by stabilizing MYC proteins. In addition to MYC, its dimerization partner MAX is also a CK2 substrate. It is worth noting that CK2-dependent phosphorylation of MAX affects the kinetics of DNA binding of both MYC/MAX hetero- and MAX/MAX homodimers and regulates the sensitivity to caspases during apoptosis (21-23). Together this suggests that CK2-dependent phosphorylation affects the stability and the DNA binding properties of MYC/MAX complexes and possibly other dimers of the network. In addition to these two areas of phosphorylation, a third is located within the TAD of MYC (Fig. 1). Two sites, Thr-58 and Ser-62 within MBI, that are targeted by GSK3 and by proline-directed kinases, respectively, have generated particular interest (24). This was stimulated at least in part by the observations that Thr-58 and amino acids in its vicinity are frequently mutated in Burkitt lymphoma (Fig. S1G) (25). The Thr-58 and Ser-62 sites are interdependent because Ser-62 phosphorylation is a prerequisite for modification of Thr-58. Kinases implicated in Ser-62 phosphorylation include mitogen-activated protein kinase (MAPK), c-JUN N-terminal kinase (JNK),
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2014-07-03T14:33:03.517+02:00
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