RT Journal Article SR Electronic T1 Differential complex formation via paralogs in the human Sin3 protein interaction network JF bioRxiv FD Cold Spring Harbor Laboratory SP 830828 DO 10.1101/830828 A1 Mark K. Adams A1 Charles A.S. Banks A1 Janet L. Thornton A1 Mihaela E. Sardiu A1 Maxime Killer A1 Cassandra G. Kempf A1 Laurence Florens A1 Michael P. Washburn YR 2019 UL http://biorxiv.org/content/early/2019/11/04/830828.abstract AB 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.APaffinity purificationAPMSaffinity purification mass spectrometryDMSOdimethyl sulfoxidedNSAFdistributed normalized spectral abundance factordSdistributed spectral countsFBSfetal bovine serumFDAFood and Drug AdministrationFDRfalse discovery rateHDAChistone deacetylaseHDACiHDAC inhibitorHIDHDAC interaction domainHPLChigh performance liquid chromatographyKDRIKazusa DNA Research InstituteMudPITmultidimensional protein identification technologyNLSnuclear localization signalPAHpaired amphipathic helixRBBP4_aRBBP4 isoform aRBBP4_cRBBP4 isoform cRFUrelative fluorescence unitsRpd3L (Sin3L)Sin3 LargeRpd3S (Sin3S)Sin3 SmallSAHAsuberoylanilide hydroxamic acidSIN3B_1SIN3B isoform 1SIN3B_2SIN3B isoform 2SIN3B_3SIN3B isoform 3