Cables1 complex couples survival signaling to the cell death machinery.

Cancer research (2014-11-02)
Zhi Shi, Hae Ryon Park, Yuhong Du, Zijian Li, Kejun Cheng, Shi-Yong Sun, Zenggang Li, Haian Fu, Fadlo R Khuri
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.

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Terbium, chips, 99.9% trace rare earth metals basis
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Terbium, foil, size 25 mm × 25 mm × 1 mm, 99.9% trace rare earth metals basis
Terbium, foil, 25x25mm, thickness 0.1mm, as rolled, 99%
Terbium, foil, 50x50mm, thickness 0.1mm, as rolled, 99%
Terbium, foil, not light tested, 25x25mm, thickness 0.025mm, as rolled, 99%
Terbium, foil, not light tested, 50x50mm, thickness 0.025mm, as rolled, 99%
Terbium, powder, 1g, max. particle size 500 micron, 99.9%
Terbium, powder, 2g, max. particle size 500 micron, 99.9%
Terbium, powder, 5g, max. particle size 500 micron, 99.9%
Terbium, rod, 100mm, diameter 6.35mm, cast, 99%
Terbium, rod, 50mm, diameter 6.35mm, cast, 99%
Terbium, wire reel, 100mm, diameter 1.0mm, hard, 99.9%
Terbium, wire reel, 50mm, diameter 1.0mm, hard, 99.9%

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