2011年2月1日 · Expression of the c-Myc oncoprotein is affected by conserved threonine 58 (T58) and serine 62 (S62) phosphorylation sites that help to regulate c-Myc protein stability, and altered ratios of T58 and S62 phosphorylation have been observed in human cancer. Here, we report the development of 3 unique c …

2022年1月28日 · We identify a second diphosphorylated degron in Myc, which synergizes with the T58 phosphodegron to bind Fbw7, and we elucidate a critical positive role of S62 phosphorylation in forming a high-affinity complex with the F-box protein. We show that the two Myc degrons are simultaneously recognized by dimeric Fbw7, which drives Myc turnover.

2020年9月7日 · In the T58A mutant, MYC is stabilized with constitutive S62 phosphorylation. When challenged with DMBA/TPA-mediated carcinogenesis, MYC T58A mice had accelerated development of papillomas,...

The full-length c-Myc was degraded by the 26S proteasome complex when the dual phosphorylated form of c-Myc (T58 and S62) was recognized, and PP2A further dephosphorylated S62. In this study, we proposed that the increasing half-life of the c-Myc (S62) protein was the key aspect in determining the stabilization of the full-length c-Myc via the ...

2020年2月18日 · First, phosphorylation of MYCN at S62, which primes the phosphorylation of T58 by GSK3 and subsequently MYCN degradation by the ubiquitin ligase SCF FBXW7, is carried out by CDK1 and hence...

2022年4月5日 · 由于苏氨酸 58 （t58） 和丝氨酸 62 （s62） 两个高度保守位点的磷酸化比率发生改变，人类癌症中致癌信号通路的破坏可以提高 myc 蛋白的稳定性。 MYC 的 T58 到丙氨酸突变体 （T58A） 模拟稳定的 S62 磷酸化和高致癌形式的 MYC。

2011年8月1日 · Myc expression is in part controlled by its protein stability, which can be regulated by phosphorylation at threonine 58 (T58) and serine 62 (S62). We now report that Myc protein stability is increased in a number of breast cancer cell lines and this correlates with increased phosphorylation at S62 and decreased phosphorylation at T58.

2022年8月15日 · Our previous study showed that the levels of c-Myc protein and the phosphorylation of threonine 58 (T58) and serine 62 (S62) increased in DSF-Cu-complex-treated oral epidermoid carcinoma Meng-1 (OECM-1) cells. These abovementioned patterns were suppressed by pretreatment with an ROS scavenger, N-acetyl cysteine.

Phosphorylation of S62 by ERK or CDK kinases transiently increases c-Myc stability while phosphorylation of T58 by GSK3β triggers dephosphorylation of S62 by protein phosphatase 2A (PP2A), ubiquitination by the SCF-Fbw7 E3 ligase and proteasomal degradation .

2022年7月6日 · Disruption of oncogenic signaling pathways in human cancers can increase MYC protein stability, due to altered phosphorylation ratios at two highly conserved sites, Threonine 58 (T58) and Serine 62 (S62). The T58 to Alanine mutant (T58A) of MYC mimics the stabilized, S62 phosphorylated, and highly oncogenic form of MYC.