alpha3beta1 integrin promotes cell survival via multiple interactions between 14-3-3 isoforms and proapoptotic proteins
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Updated: Jun 21, 2026

Identifying Protein-protein Interaction Sites Using Peptide Arrays
Published on: November 18, 2014
Ju-Eun Oh1, Da Hyun Jang, Hyunsoo Kim
1Department of Oral Biochemistry and Program of Craniomaxillofacial Reconstruction Science, Dental Research Institute, BK21 CLS, and IBEC, Seoul National University School of Dentistry, Seoul 110-749, Korea.
Abstract:
Laminin-5 and alpha3beta1 integrin promote keratinocyte survival; however, the downstream signaling pathways for laminin-5/alpha3beta1 integrin-mediated cell survival had not been fully established. We report the unexpected finding of multiple interactions between 14-3-3 isoforms and proapoptotic proteins in the survival signaling pathway. Ln5-P4 motif within human laminin-5 alpha3 chain promotes cell survival and anti-apoptosis by inactivating Bad and YAP. This effect is achieved through the formation of 14-3-3zeta/p-Bad and 14-3-3sigma/p-YAP complexes, which is initiated by alpha3beta1 integrin and FAK/PI3K/Akt signaling. These complexes result in cytoplasmic sequestration of Bad and YAP and their subsequent inactivation. An increase in Akt1 activity in cells induces 14-3-3zeta and sigma, p-Bad, and p-YAP, promoting cell survival, whereas decreasing Akt activity suppresses the same proteins and inhibits cell survival. Suppression of 14-3-3zeta with RNA-interference inhibits cell viability and promotes apoptosis. These results reveal a new mechanism of cell survival whereby the formation of 14-3-3zeta/p-Bad and 14-3-3sigma/p-YAP complexes is initiated by laminin-5 stimulation via the alpha3beta1 integrin and FAK/PI3K/Akt signaling pathways, thereby resulting in cell survival and anti-apoptosis.
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