Related Experiment Video
Updated: Aug 5, 2026
09:39
Mapping Dysfunctional Protein-Protein Interactions in Disease
Published on: October 24, 2025
ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting
Xinyi Chen1, Duo Xu1, Yongbiao Huang1
1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
International Journal of Medical Sciences
|July 29, 2026
Summary
Protein S-palmitoylation, a key cancer modification, is regulated by ZDHHC enzymes and depalmitoylases. Understanding these circuits offers new therapeutic targets for cancer progression and immune response.
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Biology
- Structural Biology
Background:
- Protein S-palmitoylation is a reversible modification crucial for cancer networks.
- ZDHHC enzymes and depalmitoylases form a dynamic circuitry controlling protein function.
- This modification links membrane topology to oncogenic, metabolic, immune, and epigenetic processes.
Purpose of the Study:
- To synthesize recent advances in structural and chemical biology of human ZDHHC enzymes.
- To clarify acyl-chain recognition and substrate engagement mechanisms.
- To discuss the rewiring of cancer-related signaling pathways by ZDHHC-substrate circuits.
Main Methods:
- Structural biology studies of ZDHHC enzymes.
- Analysis of ankyrin-repeat domains and accessory partners in substrate recruitment.
- High-throughput platform development for profiling modulators.
- Review of evidence supporting ZDHHC-substrate associations.
Main Results:
- ZDHHC enzymes possess a "tent-like" fold with a membrane-embedded cavity for acyl-chain accommodation.
- Ankyrin-repeat domains and accessory partners influence substrate recruitment and localization.
- ZDHHC-substrate circuits significantly impact growth factor signaling, metabolism, immune sensing, and chromatin regulation.
- S-palmitoylation acts as a context-dependent regulator of tumor progression, therapy response, and immune phenotype.
Conclusions:
- ZDHHC-mediated S-palmitoylation is a significant regulatory layer with potential therapeutic and biomarker relevance in cancer.
- Distinguishing robustly supported mechanisms from inferred associations is critical.
- Clinical translation is preliminary, facing challenges in selectivity, redundancy, and biomarker validation.
Related Concept Videos
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:37Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...