TY - JOUR
T1 - An Orchestrated Program Regulating Secretory Pathway Genes and Cargos by the Transmembrane Transcription Factor CREB-H
AU - Barbosa, Sónia
AU - Fasanella, Giovanna
AU - Carreira, Suzanne
AU - Llarena, Marta
AU - Fox, Rebecca
AU - Barreca, Cristina
AU - Andrew, Deborah
AU - O'Hare, Peter
PY - 2013/4
Y1 - 2013/4
N2 - CREB3 proteins comprise a set of ER-localized bZip transcription factors defined by the presence of a transmembrane domain. They are regulated by inter-compartmental transport, Golgi cleavage and nuclear transport where they promote appropriate transcriptional responses. Although CREB3 proteins play key roles in differentiation, inflammation and metabolism, a general framework relating their defining features to these diverse activities is lacking. We identify unique features of CREB3 organization including the ATB domain, which we show it is essential for transcriptional activity. This domain is absent in all other human bZip factors, but conserved in Drosophila CREBA, which controls secretory pathway genes (SPGs). Furthermore, each of the five human CREB3 factors was capable of activating SPGs in Drosophila, dependent upon the ATB domain. Expression of the CREB3 protein, CREB-H, in 293 cells, upregulated genes involved in secretory capacity, extracellular matrix formation and lipid metabolism and increased secretion of specific cargos. In liver cells, which normally express CREB-H, the active form specifically induced secretion of apolipoproteins, including ApoA-IV, ApoAI, consistent with data implicating CREB-H in metabolic homeostasis. Based on these data and other recent studies, we propose a general role for the CREB3 family in regulating secretory capacity, with particular relevance to specialized cargos.
AB - CREB3 proteins comprise a set of ER-localized bZip transcription factors defined by the presence of a transmembrane domain. They are regulated by inter-compartmental transport, Golgi cleavage and nuclear transport where they promote appropriate transcriptional responses. Although CREB3 proteins play key roles in differentiation, inflammation and metabolism, a general framework relating their defining features to these diverse activities is lacking. We identify unique features of CREB3 organization including the ATB domain, which we show it is essential for transcriptional activity. This domain is absent in all other human bZip factors, but conserved in Drosophila CREBA, which controls secretory pathway genes (SPGs). Furthermore, each of the five human CREB3 factors was capable of activating SPGs in Drosophila, dependent upon the ATB domain. Expression of the CREB3 protein, CREB-H, in 293 cells, upregulated genes involved in secretory capacity, extracellular matrix formation and lipid metabolism and increased secretion of specific cargos. In liver cells, which normally express CREB-H, the active form specifically induced secretion of apolipoproteins, including ApoA-IV, ApoAI, consistent with data implicating CREB-H in metabolic homeostasis. Based on these data and other recent studies, we propose a general role for the CREB3 family in regulating secretory capacity, with particular relevance to specialized cargos.
KW - ApoA-IV
KW - Apolipoproteins
KW - CREB-H
KW - CREB3L3
KW - CREBA
KW - Extracellular matrix
KW - Lipid metabolism
KW - Secretion
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U2 - 10.1111/tra.12038
DO - 10.1111/tra.12038
M3 - Article
C2 - 23279168
AN - SCOPUS:84874680557
SN - 1398-9219
VL - 14
SP - 382
EP - 398
JO - Traffic
JF - Traffic
IS - 4
ER -