The Proteomic Profile of Deleted in Breast Cancer 1 (DBC1) Interactions Points to a Multifaceted Regulation of Gene Expression

• DOI: 10.1074/mcp.m115.054619
• Publication Date: 2015-12-10T04:55:12Z
• Authors: Sophie S.B. Giguère; Amanda J. Guise; Pierre M. Jean Be...; Preeti M. Joshi; Todd M. Greco; Olivia L. Quach; Jeffery Kong; Ileana M. Cristea
• Keywords: Expression (computer science)

Deleted in breast cancer 1 (DBC1) has emerged as an important regulator of multiple cellular processes, ranging from gene expression to cell cycle progression. DBC1 been linked tumorigenesis both inhibitor histone deacetylases, HDAC3 and sirtuin 1, a transcriptional cofactor for nuclear hormone receptors. However, despite mounting interest DBC1, relatively little is known about the range its interacting partners scope functions. Here, we carried out functional proteomics-based investigation interactions two relevant types, T cells kidney cells. Microscopy, molecular biology, biochemistry, mass spectrometry studies allowed us assess mRNA protein levels, localization, phosphorylation status, interaction networks. The comparison these types revealed conserved regulatory roles expression, chromatin organization modification, Interestingly, observe previously unrecognized with proteins encoded by cancer-associated genes. Among are five components SWI/SNF complex, most frequently mutated remodeling complex human cancers. Additionally, identified TBL1XR1, component NCoR which validated reciprocal isolation. Strikingly, discovered that associates regulate circadian cycle, including DDX5, DHX9, SFPQ. We this colocalization Functional assessment association demonstrated levels regulating CLOCK BMAL1 oscillations synchronized Our results suggest integral maintenance clock. Furthermore, provide valuable resource exploration pathways involved DBC1-associated tumorigenesis.