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Updated: Apr 23, 2026
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Oncogenic nature of a novel mutant AATF and its interactome existing within human cancer cells
Shaveta Sharma1, Deepak Kaul, Mansi Arora
1Department of Experimental Medicine & Biotechnology, Molecular Biology Unit, Post-graduate Institute of Medical Education & Research, Chandigarh, 160012, India.
Abstract:
Since apoptosis presents a natural defense in cancer development, the anti-apoptotic factor AATF/Che-1 has emerged as a crucial 'Epigenomic-Switch'. We have tried to understand the double-edged nature of AATF, showing for the first time the conspicuous existence of an aberrant AATF/Che-1 transcriptome encoding for 23 kDa mutant AATF protein, which evolves its unique interactome within human cancer cells derived from different tissue origins. This mutant AATF along with its interactome consisting of SP1, DNMT3B and Par-4 ensures cancer cell DNA methylation required for down-regulation of tumor suppressor genes. Hence, the proposed mutant AATF interactome-based pathway can have the inherent ability to ensure human cells become and remain cancerous.
Insights
The anti-apoptotic factor AATF/Che-1 acts as an
Area of Science:
- Molecular Biology
- Cancer Biology
- Epigenetics
Background:
- Apoptosis is a natural defense against cancer development.
- The anti-apoptotic factor AATF/Che-1 is identified as a key 'Epigenomic-Switch'.
Purpose of the Study:
- To investigate the dual role of AATF/Che-1 in cancer.
- To characterize the aberrant AATF/Che-1 transcriptome and its protein product in human cancer cells.
Main Methods:
- Analysis of aberrant AATF/Che-1 transcriptome.
- Identification of the mutant AATF protein interactome in various human cancer cells.
- Investigation of DNA methylation patterns associated with the mutant AATF interactome.
Main Results:
- Discovery of a 23 kDa mutant AATF protein arising from an aberrant transcriptome.
- Identification of a unique interactome for mutant AATF, including SP1, DNMT3B, and Par-4.
- Demonstration that the mutant AATF interactome promotes DNA methylation, leading to tumor suppressor gene downregulation.
Conclusions:
- The mutant AATF interactome establishes and maintains a cancerous phenotype in human cells.
- This pathway highlights a novel mechanism by which cancer cells evade apoptosis and promote tumorigenesis.
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