Nuclear import of IκBα is accomplished by a Ran-independent transport pathway

Shrikesh Sachdev, Sriparna Bagchi, Donna Zhang, Angela C. Mings, Mark Hannink

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The inhibitor of kappa B alpha (IκBα) protein is able to shuttle between the cytoplasm and the nucleus. We have utilized a combination of in vivo and in vitro approaches to provide mechanistic insight into nucleocytoplasmic shuttling by IκBα. IκBα contains multiple functional domains that contribute to shuttling of IκBα between the cytoplasm and the nucleus. Nuclear import of IκBα is mediated by the central ankyrin repeat domain. Similar to previously described nuclear import pathways, nuclear import of IκBα is temperature and ATP dependent and is blocked by a dominant-negative mutant of importin β. However, in contrast to classical nuclear import pathways, nuclear import of IκBα is independent of soluble cytosolic factors and is not blocked by the dominant-negative RanQ69L protein. Nuclear export of IκBα is mediated by an N-terminal nuclear export sequence. Nuclear export of IκBα requires the CRM1 nuclear export receptor and is blocked by the dominant-negative RanQ69L protein. Our results are consistent with a model in which nuclear import of IκBα is mediated through direct interactions with components of the nuclear pore complex, while nuclear export of IκBα is mediated via a CRM1-dependent pathway.

Original languageEnglish (US)
Pages (from-to)1571-1582
Number of pages12
JournalMolecular and Cellular Biology
Volume20
Issue number5
DOIs
StatePublished - Mar 2000
Externally publishedYes

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Cell Nucleus Active Transport
Cytoplasm
Karyopherins
Ankyrin Repeat
Nuclear Pore
Proteins
Cytoplasmic and Nuclear Receptors
Adenosine Triphosphate

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Nuclear import of IκBα is accomplished by a Ran-independent transport pathway. / Sachdev, Shrikesh; Bagchi, Sriparna; Zhang, Donna; Mings, Angela C.; Hannink, Mark.

In: Molecular and Cellular Biology, Vol. 20, No. 5, 03.2000, p. 1571-1582.

Research output: Contribution to journalArticle

Sachdev, Shrikesh ; Bagchi, Sriparna ; Zhang, Donna ; Mings, Angela C. ; Hannink, Mark. / Nuclear import of IκBα is accomplished by a Ran-independent transport pathway. In: Molecular and Cellular Biology. 2000 ; Vol. 20, No. 5. pp. 1571-1582.
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