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MAGED 1 is a novel regulator of a select subset of bHLH PAS transcription factors
Author(s) -
Sullivan Adrienne E.,
Peet Daniel J.,
Whitelaw Murray L.
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13824
Subject(s) - aryl hydrocarbon receptor nuclear translocator , pas domain , transcription factor , basic helix loop helix , regulator , coactivator , biology , microbiology and biotechnology , function (biology) , transcription (linguistics) , transcriptional regulation , cytoplasm , genetics , dna binding protein , gene , linguistics , philosophy , aryl hydrocarbon receptor
Transcription factors of the basic helix‐loop‐helix ( bHLH ) PER ‐ ARNT ‐ SIM ( PAS ) family generally have critical and nonredundant biological roles, but some bHLH PAS proteins compete for common cofactors or recognise similar DNA elements. Identifying factors that regulate function of bHLH PAS proteins, particularly in cells where multiple family members are coexpressed, is important for understanding bHLH PAS factor biology. This study identifies and characterises a novel interaction between melanoma‐associated antigen D1 ( MAGED 1) and select members of the bHLH PAS transcription factor family. MAGED 1 binds and positively regulates the transcriptional activity of family members SIM 1, SIM 2, NPAS 4 and ARNT 2, but does not interact with AhR, HIF 1α and ARNT . This interaction is mediated by PAS repeat regions which also form the interface for bHLH PAS dimerisation, and accordingly MAGED 1 is not found in complex with bHLH PAS dimers. We show that MAGED 1 does not affect bHLH PAS protein levels and cannot be acting as a coactivator of transcriptionally active heterodimers, but rather appears to interact with nascent bHLH PAS proteins in the cytoplasm to enhance their function prior to nuclear import. As a selective regulator, MAGED 1 may play an important role in the biology of these specific factors and in general bHLH PAS protein dynamics.