TY - JOUR
T1 - Identification of a highly conserved module in E proteins required for in vivo helix-loop-helix dimerization
AU - Goldfarb, Adam N.
AU - Lewandowska, Kristine
AU - Pennell, Cristopher A.
PY - 1998/1/30
Y1 - 1998/1/30
N2 - Basic helix-loop-helix (bHLH) transcription factors often function as heterodimeric complexes consisting of a tissue-specific factor such as SCL/tal or MyoD bound to a broadly expressed E protein. bHLH dimerization therefore appears to represent a key regulatory step in cell lineage determination and oncogenesis. Previous functional and structural studies have indicated that the well defined HLH domain is both necessary and sufficient for dimerization. Most of these studies, however, have employed in vitro systems for analysis of HLH dimerization, and their implications for the requirements for in vivo dimerization remain unclear. Using multiple approaches, we have analyzed bHLH dimerization in intact, living cells and have identified a novel domain in E proteins, domain C, which is required for in vivo dimerization. Domain C, which lies just carboxyl-terminal to helix 2 of the HLH domain, represents the most highly conserved region within E proteins and appears to influence the in vivo conformation of the adjacent HLH domain. These results suggest that HLH dimerization in vivo may represent a complex, regulated process that is distinct from HLH dimerization in vitro.
AB - Basic helix-loop-helix (bHLH) transcription factors often function as heterodimeric complexes consisting of a tissue-specific factor such as SCL/tal or MyoD bound to a broadly expressed E protein. bHLH dimerization therefore appears to represent a key regulatory step in cell lineage determination and oncogenesis. Previous functional and structural studies have indicated that the well defined HLH domain is both necessary and sufficient for dimerization. Most of these studies, however, have employed in vitro systems for analysis of HLH dimerization, and their implications for the requirements for in vivo dimerization remain unclear. Using multiple approaches, we have analyzed bHLH dimerization in intact, living cells and have identified a novel domain in E proteins, domain C, which is required for in vivo dimerization. Domain C, which lies just carboxyl-terminal to helix 2 of the HLH domain, represents the most highly conserved region within E proteins and appears to influence the in vivo conformation of the adjacent HLH domain. These results suggest that HLH dimerization in vivo may represent a complex, regulated process that is distinct from HLH dimerization in vitro.
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U2 - 10.1074/jbc.273.5.2866
DO - 10.1074/jbc.273.5.2866
M3 - Article
C2 - 9446597
AN - SCOPUS:0032579271
SN - 0021-9258
VL - 273
SP - 2866
EP - 2873
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -