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Author

Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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Novel nuclear localization signal regulated by ambient tonicity in vertebrates

Cited 9 times inthomson ciCited 8 times inthomson ci
Title
Novel nuclear localization signal regulated by ambient tonicity in vertebrates
Author
Kwon, Min SeongDo Lee, SangKim, Jeong-AhColla, EmanuelaChoi, Yu JeongSuh, Pann-GhillKwon, H. Moo
Keywords
ENHANCER-BINDING PROTEIN; TRANSCRIPTION FACTOR TONEBP; SYSTEMIC HYPERTONICITY; DOWN-REGULATION; OSMOTIC-STRESS; EXPRESSION; KINASE; EXPORT; PHOSPHORYLATION; DIMERIZATION
Issue Date
200808
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.283, no.33, pp.22400 - 22409
Abstract
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.
URI
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DOI
http://dx.doi.org/10.1074/jbc.M710550200
ISSN
0021-9258
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