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Updated: Aug 19, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer
Anne Benzinger1, Nemone Muster, Heike B Koch
1Molecular Oncology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried/Munich, Germany.
Abstract:
To comprehensively identify proteins interacting with 14-3-3 sigma in vivo, tandem affinity purification and the multidimensional protein identification technology were combined to characterize 117 proteins associated with 14-3-3 sigma in human cells. The majority of identified proteins contained one or several phosphorylatable 14-3-3-binding sites indicating a potential direct interaction with 14-3-3 sigma. 25 proteins were not previously assigned to any function and were named SIP2-26 (for 14-3-3 sigma-interacting protein). Among the 92 interactors with known function were a number of proteins previously implicated in oncogenic signaling (APC, A-RAF, B-RAF, and c-RAF) and cell cycle regulation (AJUBA, c-TAK, PTOV-1, and WEE1). The largest functional classes comprised proteins involved in the regulation of cytoskeletal dynamics, polarity, adhesion, mitogenic signaling, and motility. Accordingly ectopic 14-3-3 sigma expression prevented cellular migration in a wounding assay and enhanced mitogen-activated protein kinase signaling. The functional diversity of the identified proteins indicates that induction of 14-3-3 sigma could allow p53 to affect numerous processes in addition to the previously characterized inhibitory effect on G2/M progression. The data suggest that the cancer-specific loss of 14-3-3 sigma expression by epigenetic silencing or p53 mutations contributes to cancer formation by multiple routes.
Insights
Researchers identified 117 proteins interacting with 14-3-3 sigma, revealing its broad role in cellular processes beyond cell cycle regulation. This highlights 14-3-3 sigma
Area of Science:
- Cellular Biology
- Molecular Biology
- Cancer Research
Background:
- 14-3-3 sigma is a protein involved in cell cycle regulation and apoptosis.
- Its role in other cellular processes and its interactome in vivo are not fully understood.
- Loss of 14-3-3 sigma expression is observed in various cancers.
Purpose of the Study:
- To comprehensively identify proteins interacting with 14-3-3 sigma in human cells.
- To understand the functional implications of these interactions in cellular processes and cancer.
Main Methods:
- Tandem affinity purification combined with multidimensional protein identification technology (MudPIT).
- Characterization of 117 identified 14-3-3 sigma-associated proteins.
- Functional analysis of identified interactors and assessment of 14-3-3 sigma's effect on cellular migration and signaling.
Main Results:
- Identified 117 proteins interacting with 14-3-3 sigma, with most containing potential binding sites.
- Discovered 25 novel interacting proteins (SIP2-26) and 92 known proteins involved in oncogenic signaling and cell cycle regulation.
- Identified functional classes related to cytoskeletal dynamics, polarity, adhesion, and mitogenic signaling; ectopic 14-3-3 sigma inhibited cell migration and enhanced MAPK signaling.
Conclusions:
- 14-3-3 sigma interacts with a diverse set of proteins, influencing multiple cellular processes.
- The findings suggest 14-3-3 sigma's role extends beyond cell cycle arrest, impacting cell motility and signaling.
- Cancer-associated loss of 14-3-3 sigma may contribute to tumorigenesis through various pathways.
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