NOSTRINbeta--a shortened NOSTRIN variant with a role in transcriptional regulation.
Traffic
; 10(1): 26-34, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-18980613
ABSTRACT
We recently observed that a novel, shortened variant of eNOS trafficking inducer (NOSTRIN) is expressed in cirrhotic liver. This shortened variant (NOSTRINbeta) lacks the first 78 amino acids of full-length NOSTRIN (NOSTRINalpha) and thus a substantial part of its F-BAR domain. In contrast to NOSTRINalpha, NOSTRINbeta mainly localizes to the cell nucleus. In this study, we show that nuclear import of NOSTRINbeta depends on two nuclear localization signals (aa 32-36 KKRK and aa 57-61 KAKKK). Each of the sequences is independently functional, but both are required to sustain nuclear localization of NOSTRINbeta. Export of NOSTRINbeta from the nucleus is facilitated by a CRM1-dependent mechanism relying on the nuclear export sequence LELEKERIQL (aa 135-145). Unlike NOSTRINbeta, the full-length variant NOSTRINalpha was conspicuously absent from the nucleus. This is most likely because of the fact that its N-terminal F-BAR domain, which is truncated in NOSTRINbeta, facilitates association with cellular membranes. NOSTRINbeta directly binds to the 5'-regulatory region of the NOSTRIN gene (bp -200 to -1), and overexpression of NOSTRINbeta strongly decreases transcription of a reporter gene under control of this DNA region. Taken together, our results suggest that nuclear NOSTRINbeta may negatively regulate transcription of the NOSTRIN gene.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Regulação da Expressão Gênica
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Processamento Alternativo
/
Peptídeos e Proteínas de Sinalização Intracelular
Limite:
Humans
Idioma:
En
Revista:
Traffic
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Alemanha