American Association for Cancer Research
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Supplementary References from Cables1 Complex Couples Survival Signaling to the Cell Death Machinery

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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 References. References for Supplementary Tables and Figures

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ARTICLE ABSTRACT

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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