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Cited by 331

The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking

Zeng, Xuehuo, Overmeyer, Jean H., Maltese, William A.·2006·Journal of Cell Science

Abstract

Beclin 1 was originally identified as a novel Bcl-2-interacting protein, but co-immunoprecipitation studies suggest that the major physiological partner for Beclin 1 is the mammalian class III phosphatidylinositol 3-kinase (PI 3-kinase) Vps34. Beclin 1 has been proposed to function as a tumor suppressor by promoting cellular macroautophagy, a process that is known to depend on Vps34. However, an alternative role for Beclin 1 in modulating normal Vps34-dependent protein trafficking pathways has not been ruled out. This possibility was examined in U-251 glioblastoma cells. Immunoprecipitates of endogenous Beclin 1 contained human Vps34 (hVps34), but not Bcl-2. Suppression of Beclin 1 expression by short interfering (si)RNA-mediated gene silencing blunted the autophagic response of the cells to nutrient deprivation or C2-ceramide. However, other PI 3-kinase-dependent trafficking pathways, such as the post-endocytic sorting of the epidermal growth factor receptor (EGFR) or the proteolytic processing of procathepsin D en route from the trans-Golgi network (TGN) to lysosomes, were not affected. Depletion of Beclin 1 did not reduce endocytic internalization of a fluid phase marker (horseradish peroxidase, HRP) or cause swelling of late endosomal compartments typically seen in cells where the function of hVps34 is impaired. These findings argue against a role for Beclin 1 as an essential chaperone or adaptor for hVps34 in normal vesicular trafficking, and they support the hypothesis that Beclin 1 functions mainly to engage hVps34 in the autophagic pathway.

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Metadata

Authors
Zeng, X., Overmeyer, J. H., & Maltese, W. A.
Venue
Journal of Cell Science
Published
2006-01-15
Volume
119
Issue
2
Pages
259-270
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
OpenAlex
W1978405493
Cited by
331
References
9
FWCI
19.04
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking. https://app.cochat.ai/papers/10.1242/jcs.02735
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Zeng, X., Overmeyer, J. H., & Maltese, W. A. (2006). Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking. Journal of Cell Science. https://doi.org/10.1242/jcs.02735

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