PT - JOURNAL ARTICLE AU - Mark K. Adams AU - Charles A.S. Banks AU - Janet L. Thornton AU - Mihaela E. Sardiu AU - Maxime Killer AU - Cassandra G. Kempf AU - Laurence Florens AU - Michael P. Washburn TI - Differential complex formation via paralogs in the human Sin3 protein interaction network AID - 10.1101/830828 DP - 2019 Jan 01 TA - bioRxiv PG - 830828 4099 - http://biorxiv.org/content/early/2019/11/04/830828.short 4100 - http://biorxiv.org/content/early/2019/11/04/830828.full 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