Cited by 85Autophagy in Disease and TherapyCellular transport and secretionCalcium signaling and nucleotide metabolism

NRBF2 regulates macroautophagy as a component of Vps34 Complex I

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Cao, Yanyan, Wang, Yichen, Abi Saab, Widian F., Yang, Fajun, Pessin, Jeffrey E., Backer, Jonathan M.·2014·Biochemical Journal

Abstract

Macroautophagy is a physiological cellular response to nutrient stress, which leads to the engulfment of cytosolic contents by a double-walled membrane structure, the phagophore. Phagophores seal to become autophagosomes, which then fuse with lysosomes to deliver their contents for degradation. Macroautophagy is regulated by numerous cellular factors, including the Class III PI3K (phosphoinositide 3-kinase) Vps34 (vacuolar protein sorting 34). The autophagic functions of Vps34 require its recruitment to a complex that includes Vps15, Beclin-1 and Atg14L (autophagy-related 14-like protein) and is known as Vps34 Complex I. We have now identified NRBF2 (nuclear receptor-binding factor 2) as a new member of Vps34 Complex I. NRBF2 binds to complexes that include Vps34, Vps15, Beclin-1 and ATG-14L, but not the Vps34 Complex II component UVRAG (UV radiation resistance-associated gene). NRBF2 directly interacts with Vps15 via the Vps15 WD40 domain as well as other regions of Vps15. The formation of GFP–LC3 (light chain 3) punctae and PE (phosphatidylethanolamine)-conjugated LC3 (LC3-II) in serum-starved cells was inhibited by NRBF2 knockdown in the absence and presence of lysosomal inhibitors, and p62 levels were increased. Thus NRBF2 plays a critical role in the induction of starvation-induced autophagy as a specific member of Vps34 Complex I.

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Authors
Cao, Y., Wang, Y., Abi Saab, W. F., Yang, F., Pessin, J. E., & Backer, J. M.
Affiliations
  • Albert Einstein College of Medicine (US)
  • Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, U.S.A.
Corresponding author
  • Cao, Yanyan
  • Wang, Yichen
Venue
Biochemical Journal
Published
2014-06-26
Volume
461
Issue
2
Pages
315-322
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
OpenAlex
W2312621780
Cited by
84
References
35
Citations by year
2026: 2 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 7 · 2021: 18 · 2020: 7 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 7 · 2014: 2
FWCI
6.04
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R01AG039632, AG039632)
  • National Cancer Institute (P30CA013330)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK041296, P60DK020541)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-064420, R01AR064420)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
macroautophagy, Vps34, VPS15, Beclin-1, ATG14L, UVRAG, WD40 domain, starvation-induced autophagy, LC3, p62, nutritional stress, autophagosome formation
MeSH terms
Autophagy-Related Proteins, Beclin-1, Autophagy, Gene Expression Regulation, Humans, Lysosomes, Membrane Proteins, Microtubule-Associated Proteins, Phagosomes, Vacuoles, Signal Transduction, Trans-Activators, Genes, Reporter, HSP70 Heat-Shock Proteins, Protein Transport, Mitochondrial Proteins, Tumor Suppressor Proteins, Adaptor Proteins, Vesicular Transport, RNA, Small Interfering, Green Fluorescent Proteins, Apoptosis Regulatory Proteins, HEK293 Cells, Class III Phosphatidylinositol 3-Kinases, Vacuolar Sorting Protein VPS15

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