Related Experiment Video
Updated: Feb 4, 2026
Chemical Dimerization-Induced Protein Condensates on Telomeres
Published on: April 12, 2021
Survivin/BIRC5-derived peptide disrupts survivin dimerization and cell division and induces multifaceted anti-cancer
Manikandan Santhanam1, Venkatadri Babu1, Anna Shteinfer-Kuzmine2
1Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Abstract:
Survivin, a homodimeric protein overexpressed in virtually all cancers, is largely absent in non-proliferating adult tissues. It is a multifunctional regulator of cellular homeostasis that plays critical roles in proliferation, apoptosis, and immune regulation, which are central to cancer development and progression. Using a peptide array composed of sequences from SMAC/Diablo-interacting proteins, we identified a SMAC-binding sequence within survivin. Here, we report the characterization of a 24-amino-acid peptide spanning key survivin domains: the homodimer interface, microtubule, nuclear import, and chromosomal passenger complex binding sites. The peptide binds survivin and interferes with its dimerization, disrupting interactions with itself and partner proteins such as tubulin. When engineered as stabilized cell-penetrating peptides targeted to the cytosol, mitochondria, or nucleus, they effectively inhibited proliferation, disrupted the completion of mitosis, and induced apoptosis. In lung tumor models, the peptides reduced tumor cell proliferation and growth, while activating anti-tumor immune responses. They increased CD8+ T cell and NK cell infiltration and elevated PD-1/PD-L1 expression in the tumors. Additionally, they reduced the levels of survivin, SMAC, and tubulin, while increasing p53 expression in both in vitro and in vivo models. These findings highlight a novel strategy for targeting undruggable survivin using survivin-derived engineered peptides, offering promising therapeutic potential in cancer.
Insights
Researchers developed novel peptides targeting survivin, a protein crucial in cancer. These engineered peptides inhibit cancer cell proliferation and growth, offering a promising new therapeutic strategy for various cancers.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Survivin is a protein overexpressed in most cancers, playing key roles in cell proliferation, apoptosis, and immune regulation.
- Its overexpression contributes significantly to cancer development and progression, making it a critical therapeutic target.
- Survivin's multifunctional nature and role in cellular homeostasis present challenges for conventional drug development.
Purpose of the Study:
- To identify and characterize a survivin-binding peptide derived from SMAC/Diablo-interacting sequences.
- To engineer stabilized, cell-penetrating peptides targeting survivin for cancer therapy.
- To evaluate the therapeutic efficacy of these engineered peptides in preclinical cancer models.
Main Methods:
- Peptide array screening to identify survivin-binding sequences.
- Characterization of a 24-amino-acid peptide targeting survivin domains.
- Engineering of stabilized, cell-penetrating peptides for intracellular targeting (cytosol, mitochondria, nucleus).
- In vitro and in vivo studies in lung tumor models to assess anti-cancer effects and immune responses.
Main Results:
- Identified and characterized a peptide that binds survivin and inhibits its dimerization, disrupting interactions with proteins like tubulin.
- Engineered peptides effectively inhibited cancer cell proliferation, disrupted mitosis, and induced apoptosis.
- In vivo studies showed reduced tumor growth, increased infiltration of CD8+ T cells and NK cells, and elevated PD-1/PD-L1 expression.
- Peptides reduced survivin, SMAC, and tubulin levels while increasing p53 expression.
Conclusions:
- Survivin-derived engineered peptides represent a novel therapeutic strategy for targeting the 'undruggable' survivin protein.
- These peptides demonstrate significant potential in inhibiting cancer progression and activating anti-tumor immunity.
- The findings support further development of these peptides as a promising new class of cancer therapeutics.
More Related Videos
Related Concept Videos
02:13Determining the Plane of Cell Division
Animal cells
In animal cells, the cleavage furrow forms along the plane of cell division...
01:27Molecular Factors Affecting Cell Division
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
02:43Peptide Bonds
01:26Long Division of Polynomials
01:51Mechanisms of Retrovirus-induced Cancers
01:18Directing and Steric Effects in Disubstituted Benzene Derivatives