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PMID: 10397761 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip.

Molecular biology of the cell ·Vol. 10 ·No. 7 ·1999-07-00 ·Pages 2221-33

Nagoshi E, Imamoto N, Sato R, Yoneda Y

Abstract

The sterol regulatory element-binding protein-2 (SREBP-2) is produced as a large precursor molecule attached to the endoplasmic reticulum membrane. In response to the sterol depletion, the N-terminal segment of the precursor, which contains a basic helix-loop-helix-leucine zipper domain, is released by two sequential cleavages and is translocated to the nucleus, where it activates the transcription of target genes. The data herein show that released SREBP-2 uses a distinct nuclear transport pathway, which is mediated by importin beta. The mature form of SREBP-2 is actively transported into the nucleus when injected into the cell cytoplasm. SREBP-2 binds directly to importin beta in the absence of importin alpha. Ran-GTP but not Ran-GDP causes the dissociation of the SREBP-2-importin beta complex. G19VRan-GTP inhibits the nuclear import of SREBP-2 in living cells. In the permeabilized cell in vitro transport system, nuclear import of SREBP-2 is reconstituted only by importin beta in conjunction with Ran and its interacting protein p10/NTF2. We further demonstrate that the helix-loop-helix-leucine zipper motif of SREBP-2 contains a novel type of nuclear localization signal, which binds directly to importin beta.

MeSH Terms
Binding Sites Biological Transport Cell Nucleus/metabolism DNA-Binding Proteins/genetics,metabolism HeLa Cells/metabolism Helix-Loop-Helix Motifs Humans Karyopherins Leucine Zippers Nuclear Proteins/metabolism Recombinant Proteins/genetics,metabolism Sterol Regulatory Element Binding Protein 2 Transcription Factors/genetics,metabolism ran GTP-Binding Protein
Chemicals
DNA-Binding Proteins Karyopherins Nuclear Proteins Recombinant Proteins SREBF2 protein, human Sterol Regulatory Element Binding Protein 2 Transcription Factors ran GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Nagoshi E
Department of Anatomy and Cell Biology, Osaka University Medical School, Osaka 565-0871, Japan.
Imamoto N
Sato R
Yoneda Y
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.10.7.2221
Published
1999-07-00
Pages
2221-33
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC25438
Subset
IM
Grants
NCIPC CDC HHS · U17 CE002006 · United States
External Links
PubMed source DOI: 10.1091/mbc.10.7.2221 PMC Full Text View journal details
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