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Updated: Jun 21, 2026
07:44
Identifying Protein-protein Interaction Sites Using Peptide Arrays
Published on: November 18, 2014
alpha3beta1 integrin promotes cell survival via multiple interactions between 14-3-3 isoforms and proapoptotic
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.
Experimental Cell Research
|August 18, 2009
Summary
Laminin-5 and alpha3beta1 integrin activate survival pathways by forming 14-3-3 complexes with Bad and YAP, promoting keratinocyte survival and inhibiting apoptosis.
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- Laminin-5 (Ln5) and alpha3beta1 integrin are known to promote keratinocyte survival.
- The precise downstream signaling mechanisms mediating this survival effect were not fully understood.
Purpose of the Study:
- To elucidate the downstream signaling pathways involved in Laminin-5/alpha3beta1 integrin-mediated keratinocyte survival.
- To identify novel interactions between 14-3-3 isoforms and proapoptotic proteins in this pathway.
Main Methods:
- Investigated interactions between 14-3-3 isoforms and proapoptotic proteins (Bad, YAP).
- Utilized RNA interference to suppress 14-3-3zeta expression.
- Analyzed the role of alpha3beta1 integrin, FAK/PI3K/Akt signaling in complex formation and cell survival.
Main Results:
- Discovered that the Ln5-P4 motif inactivates Bad and YAP through 14-3-3zeta/p-Bad and 14-3-3sigma/p-YAP complex formation.
- These complexes lead to cytoplasmic sequestration and inactivation of Bad and YAP.
- Increased Akt1 activity enhanced these complexes, promoting cell survival, while decreased activity inhibited them.
- Suppression of 14-3-3zeta via RNA interference led to reduced cell viability and increased apoptosis.
Conclusions:
- Revealed a novel cell survival mechanism initiated by Laminin-5 via alpha3beta1 integrin and FAK/PI3K/Akt signaling.
- Demonstrated the critical role of 14-3-3zeta/p-Bad and 14-3-3sigma/p-YAP complex formation in promoting cell survival and anti-apoptosis.
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