Disease relevance of Becn1

• Here we show that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions [1].
• The beclin 1 autophagy gene is monoallelically deleted in 40-75% of cases of human sporadic breast, ovarian, and prostate cancer [1].
• The brains of mice infected with SIN/beclin had fewer Sindbis virus RNA-positive cells, fewer apoptotic cells, and lower viral titers than the brains of mice infected with SIN/beclinDeltaBcl-2BD or SIN/beclinstop [2].
• Closed head injury induces upregulation of Beclin 1 at the cortical site of injury [3].
• These findings show that Beclin 1 may play a role in brain responses to head trauma [3].

High impact information on Becn1

• Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy [4].
• Autophagy stimulation increased phagosomal colocalization with Beclin-1, a subunit of the phosphatidylinositol 3-kinase hVPS34, necessary for autophagy and a target for mycobacterial phagosome maturation arrest [5].
• These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression [1].
• Furthermore, beclin 1 heterozygous disruption results in increased cellular proliferation and reduced autophagy in vivo [1].
• We show here that beclin 1-/- mutant mice die early in embryogenesis and beclin 1+/- mutant mice suffer from a high incidence of spontaneous tumors [6].

Biological context of Becn1

• Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers [1].
• The biochemical properties of beclin 1 suggest a role in two fundamentally important cell biological pathways: autophagy and apoptosis [6].
• Th2 cells become more resistant to growth factor-withdrawal cell death when autophagy is blocked using either chemical inhibitors 3-methyladenine, or by RNA interference knockdown of beclin 1 and Atg7 [7].
• We identified a novel 60-kDa coiled-coil protein, Beclin, which we confirmed interacts with Bcl-2 in mammalian cells, using fluorescence resonance energy transfer microscopy [2].
• Here we demonstrate that the accumulation of mutant Huntingtin is highly sensitive to the expression of beclin 1, a gene essential for autophagy [8].

Anatomical context of Becn1

• Beclin 1-/- embryonic stem cells have a severely altered autophagic response, whereas their apoptotic response to serum withdrawal or UV light is normal [6].
• In addition, Beclin-1 expression after injury is elevated also in astrocytes starting at 3 days after injury [3].
• Confocal microscopy analysis suggests that the high levels of Beclin 1 protein in astrocytes is confined to subcellular organelles, probably lysosomes or autophagosomes [3].

Physical interactions of Becn1

• MyD88 and Trif co-immunoprecipitate with Beclin 1, a key factor in autophagosome formation [9].

Regulatory relationships of Becn1

• Autophagic death required the genes ATG7 and beclin 1 and was induced by caspase-8 inhibition [10].

Other interactions of Becn1

• Beclin 1, a Bcl2 interacting protein, was found to promote autophagy [3].

Analytical, diagnostic and therapeutic context of Becn1

• Double staining of Beclin 1 and TUNEL indicate that most of the injured cells that exhibit double staining are neurons and not astrocytes [3].
• Induction of autophagy and cardiac injury during the reperfusion phase was significantly attenuated in beclin 1(+/-) mice [11].

References