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
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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Cites
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
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“Once it is associated with the membrane, hVps34 presumably generates the PtdIns(3)P required for membrane association of FYVE-domain proteins such as the Rab effectors EEA1 and Rabenosyn-5 (Simonsen et al., 1998; De Renzis et al., 2002), and the PtdIns(3)P 5-kinase PIKfyve (Ikonomov et al., 2003).”
BackgroundThe phosphatidylinositol 3‐phosphate‐binding FYVE finger
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Cited by
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
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An Overview of Autophagy: Morphology, Mechanism, and Regulation
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Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.-I., Natsume, T., Takehana, K., Yamada, N., et al. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1248 · Cited by 2,076
Regulation of Mammalian Autophagy in Physiology and Pathophysiology
Ravikumar, B., Sarkar, S., Davies, J. E., Futter, M., Garcia-Arencibia, M., Green-Thompson, Z. W., Jimenez-Sanchez, M., Korolchuk, V. I., Lichtenberg, M., Luo, S., et al. (2010) · Physiological Reviews · doi:10.1152/physrev.00030.2009 · Cited by 1,727
Metadata
- Authors
- Zeng, X., Overmeyer, J. H., & Maltese, W. A.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- 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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- 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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