American Association for Cancer Research
00085472can140036-sup-125111_1_supp_0_ndyvgs.pdf (166.4 kB)

Supplementary Figure S1 from Cables1 Complex Couples Survival Signaling to the Cell Death Machinery

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journal contribution
posted on 2023-03-30, 23:01 authored by Zhi Shi, Hae R. Park, Yuhong Du, Zijian Li, Kejun Cheng, Shi-Yong Sun, Zenggang Li, Haian Fu, Fadlo R. Khuri

Supplementary Figure S1. Correlation of Akt status with phosphorylation of Cables1 at pT44 and T150 in an A549 tumor xenograft mouse model.



Cables1 is a candidate tumor suppressor that negatively regulates cell growth by inhibiting cyclin-dependent kinases. Cables1 expression is lost frequently in human cancer but little is known about its regulation. Here, we report that Cables1 levels are controlled by a phosphorylation and 14-3-3–dependent mechanism. Mutagenic analyses identified two residues, T44 and T150, that are specifically critical for 14-3-3 binding and that serve as substrates for phosphorylation by the cell survival kinase Akt, which by binding directly to Cables1 recruits 14-3-3 to the complex. In cells, Cables1 overexpression induced apoptosis and inhibited cell growth in part by stabilizing p21 and decreasing Cdk2 kinase activity. Ectopic expression of activated Akt (AKT1) prevented Cables1-induced apoptosis. Clinically, levels of phosphorylated Cables1 and phosphorylated Akt correlated with each other in human lung cancer specimens, consistent with pathophysiologic significance. Together, our results illuminated a dynamic regulatory system through which activated Akt and 14-3-3 work directly together to neutralize a potent tumor suppressor function of Cables1. Cancer Res; 75(1); 147–58. ©2014 AACR.

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