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bioRxiv · 10.1101/830828

Differential complex formation via paralogs in the human Sin3 protein interaction network.

Adams, M. K.·Banks, C.·Thornton, J. L.·Sardiu, M.·Killer, M.·Kempf, C.·Florens, L.·Washburn, M.
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Abstract

Despite the continued analysis of HDAC inhibitor efficacy in clinical trials, the heterogeneous nature of the protein complexes they target limits our understanding of the beneficial and off-target effects associated with their application. Among the many HDAC protein complexes found within the cell, Sin3 complexes are conserved from yeast to humans and likely play important roles as regulators of transcriptional activity. The functional attributes of these protein complexes remain poorly characterized in humans. Contributing to the poor definition of Sin3 complex attributes in higher eukaryotes is the presence of two Sin3 scaffolding proteins, SIN3A and SIN3B. Here we show that paralog switching influences the interaction networks of the Sin3 complexes. While SIN3A and SIN3B do have unique interaction network components, we find that SIN3A and SIN3B interact with a common set of proteins. Additionally, our results suggest that SIN3A and SIN3B may possess the capacity to form hetero-oligomeric complexes. While one principal form of SIN3B exists in humans, the analysis of rare SIN3B proteoforms provides insight into the domain organization of SIN3B. Together, these findings shed light on the shared and divergent properties of human Sin3 proteins and highlight the heterogeneous nature of the complexes they organize.

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Adams, M. K., Banks, C., Thornton, J. L., Sardiu, M., Killer, M., Kempf, C., Florens, L., Washburn, M.. 2019-11-04. Differential complex formation via paralogs in the human Sin3 protein interaction network.. https://doi.org/10.1101/830828

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