Differential Complex Formation via Paralogs in the Human Sin3 Protein Interaction Network

Despite the continued analysis of HDAC inhibitors 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 c...

Full description

Saved in:
Bibliographic Details
Published inMolecular & cellular proteomics Vol. 19; no. 9; p. 1468
Main Authors Adams, Mark K, Banks, Charles A S, Thornton, Janet L, Kempf, Cassandra G, Zhang, Ying, Miah, Sayem, Hao, Yan, Sardiu, Mihaela E, Killer, Maxime, Hattem, Gaye L, Murray, Alexis, Katt, Maria L, Florens, Laurence, Washburn, Michael P
Format Journal Article
LanguageEnglish
Published United States 01.09.2020
Subjects
systems biology
protein complex analysis
nuclear translocation
subcellular analysis
cross linking
Chromatin function or biology
DSSO
pathway analysis
SIN3
histone deacetylase
epigenetics
protein-protein interactions
Online AccessGet full text

Cover

More Information
Summary:Despite the continued analysis of HDAC inhibitors 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 presence of two Sin3 paralogs in humans, SIN3A and SIN3B, may result in a heterogeneous population of Sin3 complexes and contributes to our poor understanding of the functional attributes of these complexes. Here, we profile the interaction networks of SIN3A and SIN3B to gain insight into complex composition and organization. In accordance with existing data, we show that Sin3 paralog identity influences complex composition. Additionally, chemical cross-linking MS identifies domains that mediate interactions between Sin3 proteins and binding partners. The characterization of rare SIN3B proteoforms provides additional evidence for the existence of conserved and divergent elements within human Sin3 proteins. Together, these findings shed light on both the shared and divergent properties of human Sin3 proteins and highlight the heterogeneous nature of the complexes they organize.
ISSN:1535-9484