KCTD Proteins Have Redundant Functions in Controlling Cellular Growth
Robert Rizk1, Dominic Devost1, Darlaine Pétrin1
1Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Room 1303, Montréal, QC H3G 1Y6, Canada.
International Journal of Molecular Sciences
|May 11, 2024
Summary
This study reveals that KCTD2, KCTD5, and KCTD17 proteins have overlapping functions crucial for cell survival and proliferation. Their combined absence significantly impacts cell growth and gene expression, highlighting a key role in cellular homeostasis.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Potassium Channel Tetramerization Domain (KCTD) proteins are structurally related.
- Functional redundancy among KCTD protein family members is not well understood.
- The role of KCTD proteins in cellular processes like growth and gene expression requires further investigation.
Purpose of the Study:
- To investigate the functional redundancy of KCTD2, KCTD5, and KCTD17 proteins.
- To determine the impact of progressive knockout of these KCTD isoforms on cell growth and gene expression.
- To elucidate the relationship between KCTD proteins and Gβ1 in transcriptional regulation.
Main Methods:
- CRISPR/Cas9 genome editing was employed to progressively knock out KCTD2, KCTD5, and KCTD17 in HEK 293 cells.
- Validated knockout efficiency was confirmed.
- Cell growth and gene expression patterns were assessed following progressive KCTD isoform knockout.
- Gene expression profiles were compared between GNB1 knockout and KCTD knockout cells.
Main Results:
- Progressive knockout of KCTD isoforms, especially the triple knockout, significantly affected cell growth, indicating conserved functions.
- Gene expression patterns showed progressive changes correlating with KCTD isoform knockout.
- GNB1 knockout altered expression of other G protein subunit genes, whereas KCTD knockout had an opposing effect, suggesting regulation of Gβ1 levels.
- A unique relationship between KCTD proteins and Gβ1 was identified.
Conclusions:
- This subfamily of KCTD proteins plays a global role in maintaining cell survival and proliferation.
- KCTD proteins are involved in regulating Gβ1 levels, impacting transcriptional control.
- Functional redundancy exists among KCTD2, KCTD5, and KCTD17 proteins.
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