Abstract
Class III phosphatidylinositol 3-kinase (PI3KC3) plays a pleiotropic role in autophagy and protein sorting pathways. The human core complex of PI3KC3 consists of three major components including PI3KC3/hVps34, p150 and Beclin 1. How the specificity of PI3KC3 complex is derived towards autophagy is not clear. Utilizing a sequential affinity purification coupled with mass spectrometry approach, we have successfully purified a human Beclin 1 complex and cloned a novel protein we called Barkor (Beclin 1-associated autophagy-related key regulator). The function of Barkor in autophagy has been manifested in several assays, including stress-induced LC3 lipidation, autophagosome formation and Salmonella typhimurium amplification. Mechanistically, Barkor competes with UV radiation resistance associated gene product (UVRAG) for interaction with Beclin 1, and orients Beclin 1 to autophagosomes. Barkor shares considerable sequence homology with Atg14 in yeast, representing an evolutionary conserved autophagy specific regulatory step in early autophagosome formation.
Original language | English (US) |
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Pages (from-to) | 713-716 |
Number of pages | 4 |
Journal | Autophagy |
Volume | 5 |
Issue number | 5 |
DOIs | |
State | Published - Jul 1 2009 |
Keywords
- Atg14
- Autophagosome
- Autophagy
- Beclin 1
- Cancer
- PI3KC3
- Phosphatidylinositol 3-kinase
- UVRAG
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology