Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function

Huan Liang Xiao Huan Liang, J. Yu, K. Brown, B. Levine

Research output: Contribution to journalArticle

208 Citations (Scopus)

Abstract

Beclin 1 encodes a Bcl-2-interacting coiled-coil protein with autophagy and tumor suppressor function and is monoallelically deleted in 40-75% of sporadic human breast and ovarian cancers. Beclin 1 contains a leucinerich nuclear export signal motif raising the possibility that its autophagy and/or tumor suppressor function may require regulated, CRM1-dependent, nucleocytoplasmic transport. In this study, we show that wild-type Beclin 1 colocalizes with both intracytoplasmic organelles and nuclei in COS7 monkey kidney and MCF7 human breast carcinoma cells. Inhibition of CRM1-dependent nuclear export with leptomycin B or mutation of the nuclear export signal motif of Beclin 1 results in predominantly nuclear localization. Unlike wild-type Beclin 1, the nuclear export mutant of Beclin 1 fails to promote nutrient deprivation-induced autophagy and fails to inhibit in vitro clonigenicity and in vivo tumorigenicity of MCF7 cells. Thus, beclin 1 has a leptomycin B-sensitive leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function. These findings suggest that the CRM1 nuclear export pathway may be important in the functional regulation of autophagic growth control.

Original languageEnglish (US)
Pages (from-to)3443-3449
Number of pages7
JournalCancer Research
Volume61
Issue number8
StatePublished - Apr 15 2001

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Nuclear Export Signals
Autophagy
Leucine
Cell Nucleus Active Transport
Neoplasms
Breast Neoplasms
MCF-7 Cells
Beclin-1
Organelles
Ovarian Neoplasms
Haplorhini
Kidney
Food
Mutation
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function. / Xiao Huan Liang, Huan Liang; Yu, J.; Brown, K.; Levine, B.

In: Cancer Research, Vol. 61, No. 8, 15.04.2001, p. 3443-3449.

Research output: Contribution to journalArticle

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