A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export

Implications for tumorigenesis

Errol Craig, Zhi Kai Zhang, Kelvin Davies, Ganjam V. Kalpana

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

INI1 (integrase interactor 1)/hSNF5 is a component of the mammalian SWI/SNF complex and a tumor suppressor mutated in malignant rhabdoid tumors (MRT). We have identified a nuclear export signal (NES) in the highly conserved repeat 2 domain of INI1 that is unmasked upon deletion of a downstream sequence. Mutation of conserved hydrophobic residues within the NES, as well as leptomycin B treatment abrogated the nuclear export. Full-length INI1 specifically associated with hCRM1/exportin1 in vivo and in vitro. A mutant INI1 [INI1(1-319) delG950] found in MRT lacking the 66 C-terminal amino acids mislocalized to the cytoplasm. Full-length INI1 but not the INI1(1-319 delG950) mutant caused flat cell formation and cell cycle arrest in cell lines derived from MRT. Disruption of the NES in the delG950 mutant caused nuclear localization of the protein and restored its ability to cause cell cycle arrest. These observations demonstrate that INI1 has a masked NES that mediates regulated hCRM1/exportin1-dependent nuclear export and we propose that mutations that cause deregulated nuclear export of the protein could lead to tumorigenesis.

Original languageEnglish (US)
Pages (from-to)31-42
Number of pages12
JournalEMBO Journal
Volume21
Issue number1-2
DOIs
StatePublished - Jan 15 2002

Fingerprint

Nuclear Export Signals
Integrases
Cell Nucleus Active Transport
Carcinogenesis
Rhabdoid Tumor
Tumors
Cells
Nuclear Proteins
Cell Cycle Checkpoints
Mutation
Cytoplasm
Proteins
Amino Acids
Cell Line

Keywords

  • HSNF5
  • INI1
  • NES
  • Nuclear export
  • Tumor suppressor

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export : Implications for tumorigenesis. / Craig, Errol; Zhang, Zhi Kai; Davies, Kelvin; Kalpana, Ganjam V.

In: EMBO Journal, Vol. 21, No. 1-2, 15.01.2002, p. 31-42.

Research output: Contribution to journalArticle

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