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DNA Damage Induced 14-3-3Sigma Signaling

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The 14-3-3 proteins comprise a large family of highly conserved, small, acidic polypeptides of 28¡V33 kDa that are found in all eukaryotic species and play important roles in a wide range of cellular processes including signal transduction, apoptosis, cell cycle progression, and checkpoint activation (Ref.1). In humans, seven different genes encode the highly conserved 14-3-3 isotypes (Alpha, Beta, Gamma, Delta, Epsilon, Eta, Sigma, Tau, and Zeta, with Alpha and Delta being phosphorylated forms of Beta and Zeta). The 14-3-3 proteins regulate numerous cellular signaling circuits that are implicated in cancer development. They bind to protein ligands¡X following their serine/threonine phosphorylation at a defined motif¡Xand regulate their activities by a number of different mechanisms. These include inter- and intracompartmental sequestration, activation/inactivation [...]


1.Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216.
Peng CY, Graves PR, Thoma RS, Wu Z, Shaw AS, Piwnica-Worms H.
Science. 1997 Sep 5; 277(5331): 1501-5.
2.DNA damage and replication checkpoints in fission yeast require nuclear exclusion of the Cdc25 phosphatase via 14-3-3 binding.
Zeng Y, Piwnica-Worms H.
Mol Cell Biol. 1999 Nov; 19(11): 7410-9.
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