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Calreticulin Is a receptor for nuclear export.
Holaska, J M; Black, B E; Love, D C; Hanover, J A; Leszyk, J; Paschal, B M.
Afiliação
  • Holaska JM; Center for Cell Signaling, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
J Cell Biol ; 152(1): 127-40, 2001 Jan 08.
Article em En | MEDLINE | ID: mdl-11149926
In previous work, we used a permeabilized cell assay that reconstitutes nuclear export of protein kinase inhibitor (PKI) to show that cytosol contains an export activity that is distinct from Crm1 (Holaska, J.M., and B.M. Paschal. 1995. Proc. Natl. Acad. Sci. USA. 95: 14739-14744). Here, we describe the purification and characterization of the activity as calreticulin (CRT), a protein previously ascribed to functions in the lumen of the ER. We show that cells contain both ER and cytosolic pools of CRT. The mechanism of CRT-dependent export of PKI requires a functional nuclear export signal (NES) in PKI and involves formation of an export complex that contains RanGTP. Previous studies linking CRT to downregulation of steroid hormone receptor function led us to examine its potential role in nuclear export of the glucocorticoid receptor (GR). We found that CRT mediates nuclear export of GR in permeabilized cell, microinjection, and transfection assays. GR export is insensitive to the Crm1 inhibitor leptomycin B in vivo, and it does not rely on a leucine-rich NES. Rather, GR export is facilitated by its DNA-binding domain, which is shown to function as an NES when transplanted to a green fluorescent protein reporter. CRT defines a new export pathway that may regulate the transcriptional activity of steroid hormone receptors.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ribonucleoproteínas / Proteínas de Ligação ao Cálcio / Núcleo Celular / Receptores Citoplasmáticos e Nucleares / Peptídeos e Proteínas de Sinalização Intracelular Limite: Humans Idioma: En Ano de publicação: 2001 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ribonucleoproteínas / Proteínas de Ligação ao Cálcio / Núcleo Celular / Receptores Citoplasmáticos e Nucleares / Peptídeos e Proteínas de Sinalização Intracelular Limite: Humans Idioma: En Ano de publicação: 2001 Tipo de documento: Article