TY - JOUR
T1 - A small-scale survey identifies selective and quantitative nucleo-cytoplasmic shuttling of a subset of CREM transcription factors
AU - Fenaroli, Angelia
AU - Vujanac, Milos
AU - De Cesare, Dario
AU - Zimarino, Vincenzo
PY - 2004/9/10
Y1 - 2004/9/10
N2 - Elucidating dynamic aspects of intracellular localization of proteins is essential to decipher their functional interaction networks. Although transcription factors lacking a detectable cytoplasmic fraction have been generally considered compartmentalized in the nucleus, some were found to shuttle into the cytoplasm, suggesting functional interactions therein. To further investigate how common, specific and quantitative is this traffic, we have employed the heterokaryon assay for a small-scale survey of nuclear factors not previously tested for their nucleo-cytoplasmic motion. We show that a subset of cAMP response element (CRE) binding proteins of the CREM type shuttles within a biologically meaningful time frame, revealing a continuous flow into the cytoplasm that persists during signaling. Their dynamic behavior, not involving the classical Exportin-1 pathway, could be ascribed to C-terminal sequences, containing, in addition to the bZIP domain and the NLS, a nuclear export activity and an inhibitory activity at an adjacent site. Other proteins examined in this study either did not shuttle significantly or, like CREB and distinct CREM isoforms, shuttled with markedly delayed kinetics, denoting considerable selectivity of this traffic. These findings raise the possibility that events associated with bi-directional transport and periodic transit through the cytoplasm may modulate activities of select nuclear transcription factors.
AB - Elucidating dynamic aspects of intracellular localization of proteins is essential to decipher their functional interaction networks. Although transcription factors lacking a detectable cytoplasmic fraction have been generally considered compartmentalized in the nucleus, some were found to shuttle into the cytoplasm, suggesting functional interactions therein. To further investigate how common, specific and quantitative is this traffic, we have employed the heterokaryon assay for a small-scale survey of nuclear factors not previously tested for their nucleo-cytoplasmic motion. We show that a subset of cAMP response element (CRE) binding proteins of the CREM type shuttles within a biologically meaningful time frame, revealing a continuous flow into the cytoplasm that persists during signaling. Their dynamic behavior, not involving the classical Exportin-1 pathway, could be ascribed to C-terminal sequences, containing, in addition to the bZIP domain and the NLS, a nuclear export activity and an inhibitory activity at an adjacent site. Other proteins examined in this study either did not shuttle significantly or, like CREB and distinct CREM isoforms, shuttled with markedly delayed kinetics, denoting considerable selectivity of this traffic. These findings raise the possibility that events associated with bi-directional transport and periodic transit through the cytoplasm may modulate activities of select nuclear transcription factors.
KW - CRE-binding proteins
KW - Nuclear transport
KW - Nucleo-cytoplasmic shuttling
KW - Transcription factors
UR - http://www.scopus.com/inward/record.url?scp=4043119733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4043119733&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2004.05.012
DO - 10.1016/j.yexcr.2004.05.012
M3 - Article
C2 - 15302588
AN - SCOPUS:4043119733
VL - 299
SP - 209
EP - 226
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -