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Survival-promoting functions of 14-3-3 proteins
S C Masters1, R R Subramanian, A Truong
1Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.
Abstract:
The 14-3-3 proteins are a family of phosphoserine/phosphothreonine-binding molecules that control the function of a wide array of cellular proteins. We suggest that one function of 14-3-3 is to support cell survival. 14-3-3 proteins promote survival in part by antagonizing the activity of associated proapoptotic proteins, including Bad and apoptosis signal-regulating kinase 1 (ASK1). Indeed, expression of 14-3-3 inhibitor peptides in cells is sufficient to induce apoptosis. Interestingly, these 14-3-3 antagonist peptides can sensitize cells for effective killing by anticancer agents such as cisplatin. Thus, 14-3-3 may be part of the cellular machinery that maintains cell survival, and targeting 14-3-3-ligand interactions may be a useful strategy to enhance the efficacy of conventional anticancer agents.
Insights
14-3-3 proteins support cell survival by inhibiting proapoptotic proteins. Targeting these interactions may enhance cancer therapy effectiveness.
Area of Science:
- Cellular biology
- Molecular mechanisms of cell survival and apoptosis
Background:
- 14-3-3 proteins are crucial regulators of cellular processes.
- They bind phosphoserine/phosphothreonine motifs on target proteins.
- Their role in cell survival is an area of active investigation.
Purpose of the Study:
- To investigate the role of 14-3-3 proteins in cell survival.
- To explore the potential of targeting 14-3-3 proteins in cancer therapy.
Main Methods:
- Utilized 14-3-3 inhibitor peptides in cellular models.
- Assessed the impact of inhibitor peptides on apoptosis.
- Examined the combined effect of inhibitor peptides and anticancer agents.
Main Results:
- 14-3-3 proteins were found to promote cell survival.
- Inhibitor peptides induced apoptosis, sensitizing cells to killing.
- Antagonizing 14-3-3 activity enhanced the efficacy of cisplatin.
Conclusions:
- 14-3-3 proteins are integral to cellular machinery maintaining survival.
- Targeting 14-3-3-ligand interactions presents a viable strategy.
- This approach could improve the effectiveness of conventional anticancer drugs.