Related Experiment Video
Updated: Jul 14, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Ser18 and Ser23 phosphorylation plays synergistic roles in activating p53-dependent neuronal apoptosis
Jeremy Song1, Connie Chao, Yang Xu
1Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093-0322, USA.
Abstract:
Tumor suppressor p53 is required for the neuronal apoptosis in response to DNA double-stranded break (DSB) damage. Posttranslational modifications such as phosphorylation play important roles in activating p53-dependent apoptosis after DNA damage. In support of this notion, our recent studies indicate that Ser18 and Ser23 phosphorylation together plays critical roles in activating p53 apoptotic activities in vivo. Thymocytes derived from p53(S18/23A) mice are essentially resistant to p53-dependent apoptosis after DNA DSB damage. In addition, identical to p53-deficiency, p53(S18/23A) knock-in mutation completely rescues the embryonic lethality of XRCC4(-/-) mice, which die of the massive p53-dependent apoptosis of embryonic neurons likely as a result of accumulated endogenous DNA damage. To dissect the contribution of Ser18 and Ser23 phosphorylation to p53-dependent neuronal apoptosis, we report here that neither p53(S18A) nor p53(S23A) mutation alone can rescue the embryonic lethality of XRCC4(-/-) mice. Therefore, Ser18 and Ser23 phosphorylation plays synergistic and critical roles in activating p53-dependent neuronal apoptosis.
Related Concept Videos
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Abnormal Proliferation
The Intrinsic Apoptotic Pathway
Negative Regulator Molecules
DNA Damage Can Stall the Cell Cycle
DNA Damage can Stall the Cell Cycle

