Novel nuclear localization signal regulated by ambient tonicity in vertebrates.
TonEBP is a Rel domain-containing transcription factor implicated in adaptive immunity, viral replication, and cancer. In the mammalian kidney, TonEBP is a central regulator of water homeostasis. Animals deficient in TonEBP suffer from life-threatening dehydration due to renal water loss. Ambient tonicity (effective osmolality) is the prominent signal for TonEBP in a bidirectional manner; TonEBP activity decreases in hypotonicity, whereas it increases in hypertonicity. Here we found that TonEBP displayed nuclear export in response to hypotonicity and nuclear import in response to hypertonicity. The nuclear export of TonEBP was not mediated by the nuclear export receptor CRM1 or discrete nuclear export signal. In contrast, a dominant nuclear localization signal (NLS) was found in a small region of 16 amino acid residues. When short peptides containing the NLS were fused to constitutively cytoplasmic proteins, the fusion proteins displayed tonicity-dependent nucleocytoplasmic trafficking like TonEBP. Thus, tonicity-dependent activation of the NLS is crucial in the nucleocytoplasmic trafficking of TonEBP. The novel NLS is present only in the vertebrates, indicating that it developed late in evolution.
Kwon
Min Seong
MS
Department of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
Lee
Sang Do
SD
Kim
Jeong-Ah
JA
Colla
Emanuela
E
Choi
Yu Jeong
YJ
Suh
Pann-Ghil
PG
Kwon
H Moo
HM
D000818:Animals; D019556:COS Cells; D002455:Cell Division; D002467:Cell Nucleus / Q000502:physiology*; D002522:Chlorocebus aethiops; D000882:Haplorhini; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D050778:NFATC Transcription Factors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014714:Vertebrates / Q000502:physiology*
D050778:NFATC Transcription Factors