A research team at KAIST has identified the core gene expression networks regulated by key proteins that fundamentally drive phenomena such as cancer development, metastasis, tissue differentiation from stem cells, and neural activation processes. This discovery lays the foundation for developing innovative therapeutic technologies.
A joint research team led by Professors Seyun Kim, Gwangrog Lee, and Won-Ki Cho from the Department of Biological Sciences has uncovered essential mechanisms controlling gene expression in animal cells.
The findings were published on January 7 in the journal Nucleic Acids Research in a paper titled “Single-molecule analysis reveals that IPMK enhances the DNA-binding activity of the transcription factor SRF.”
Inositol phosphate metabolites produced by inositol metabolism enzymes serve as vital secondary messengers in eukaryotic cell signaling systems and are broadly implicated in cancer, obesity, diabetes, and neurological disorders.
The research team demonstrated that the inositol polyphosphate multikinase (IPMK) enzyme, a key player in the inositol metabolism system, acts as a critical transcriptional activator within the core gene expression networks of animal cells. Notably, although IPMK was previously reported to play an important role in the transcription process governed by serum response factor (SRF), a representative transcription factor in animal cells, the precise mechanism of its action was unclear.
SRF is a transcription factor directly controlling the expression of at least 200–300 genes, regulating cell growth, proliferation, apoptosis, and motility, and is indispensable for organ development, such as in the heart.
The team discovered that IPMK binds directly to SRF, altering the three-dimensional structure of the SRF protein. This interaction facilitates the transcriptional activity of various genes through the SRF activated by IPMK, demonstrating that IPMK acts as a critical regulatory switch to enhance SRF’s protein activity.
The team further verified that disruptions in the direct interaction between IPMK and SRF lead to the reduced functionality and activity of SRF, causing severe impairments in gene expression.
By highlighting the significance of the intrinsically disordered region (IDR) in SRF, the researchers underscored the biological importance of intrinsically disordered proteins (IDPs). Unlike most proteins that adopt distinct structures through folding, IDPs, including those with IDRs, do not exhibit specific structures but play crucial biological roles, attracting significant attention in the scientific community.
Professor Seyun Kim commented, “This study provides a vital mechanism proving that IPMK, a key enzyme in the inositol metabolism system, is a major transcriptional activator in the core gene expression network of animal cells.
“By understanding fundamental processes such as cancer development and metastasis, tissue differentiation from stem cells, and neural activation through SRF, we hope this discovery will lead to the broad application of innovative therapeutic technologies.”
More information:
Hyoungjoon Ahn et al, Single-molecule analysis reveals that IPMK enhances the DNA-binding activity of the transcription factor SRF, Nucleic Acids Research (2025). DOI: 10.1093/nar/gkae1281
Citation:
Researchers uncover principles of gene expression regulation in cancer and cellular functions (2025, January 24)
retrieved 25 January 2025
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