Biology:BECN1
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Beclin-1 is a protein that in humans is encoded by the BECN1 gene.[1][2] Beclin-1 is a mammalian ortholog of the yeast autophagy-related gene 6 (Atg6) and BEC-1 in the C. elegans nematode.[3] This protein interacts with either BCL-2 or PI3k class III, playing a critical role in the regulation of both autophagy and cell death.
Role in disease
Beclin-1 plays an important role in tumorigenesis, and neurodegeneration, being implicated in the autophagic programmed cell death.[4] Ovarian cancer with upregulated autophagy has a less aggressive behavior and is more responsive to chemotherapy.[5]
Schizophrenia is associated with low levels of Beclin-1 in the hippocampus of those affected, which causes diminished autophagy which in turn results in increased neuronal cell death.[6]
Interactions
BECN1 has been shown to interact with:
Modulators
- Trehalose
- Trehalose reduces p62/Beclin-1 ratio and increases autophagy in the frontal cortex of ICR mice, possibly by increasing Beclin-1.[10]
References
- ↑ 1.0 1.1 "Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein". Journal of Virology 72 (11): 8586–96. November 1998. doi:10.1128/JVI.72.11.8586-8596.1998. PMID 9765397.
- ↑ "Entrez Gene: BECN1 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8678.
- ↑ "Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans". Current Biology 15 (16): 1513–7. August 2005. doi:10.1016/j.cub.2005.07.035. PMID 16111945.
- ↑ "Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex". Nature Cell Biology 11 (4): 468–76. April 2009. doi:10.1038/ncb1854. PMID 19270693.
- ↑ 5.0 5.1 "Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer". BioMed Research International 2014: 462658. 2014. doi:10.1155/2014/462658. PMID 25136588.
- ↑ "Autophagy has a key role in the pathophysiology of schizophrenia". Molecular Psychiatry 20 (1): 126–32. February 2015. doi:10.1038/mp.2013.174. PMID 24365867.*Lay summary in: "New molecular discovery provides clues to cause of schizophrenia". January 1, 2014. http://www.medicalnewstoday.com/articles/270725.php.
- ↑ "Differential interactions between Beclin 1 and Bcl-2 family members". Autophagy 3 (6): 561–8. 2007. doi:10.4161/auto.4713. PMID 17643073.
- ↑ "A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice". Neuron 35 (5): 921–33. August 2002. doi:10.1016/S0896-6273(02)00861-9. PMID 12372286.
- ↑ 9.0 9.1 Chang, Chunmei; Young, Lindsey N.; Morris, Kyle L.; von Bülow, Sören; Schöneberg, Johannes; Yamamoto-Imoto, Hitomi; Oe, Yukako; Yamamoto, Kentaro et al. (2019-01-17). "Bidirectional Control of Autophagy by BECN1 BARA Domain Dynamics". Molecular Cell 73 (2): 339–353.e6. doi:10.1016/j.molcel.2018.10.035. ISSN 1097-4164. PMID 30581147.
- ↑ "Trehalose induced antidepressant-like effects and autophagy enhancement in mice". Psychopharmacology 229 (2): 367–75. September 2013. doi:10.1007/s00213-013-3119-4. PMID 23644913.
Further reading
- "The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond". Trends in Cell Biology 20 (6): 355–62. June 2010. doi:10.1016/j.tcb.2010.03.002. PMID 20356743.
- "Generation of a transcription map at the HSD17B locus centromeric to BRCA1 at 17q21". Genomics 28 (3): 530–42. August 1995. doi:10.1006/geno.1995.1185. PMID 7490091.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21". Genomics 59 (1): 59–65. July 1999. doi:10.1006/geno.1999.5851. PMID 10395800.
- "Induction of autophagy and inhibition of tumorigenesis by beclin 1". Nature 402 (6762): 672–6. December 1999. doi:10.1038/45257. PMID 10604474. Bibcode: 1999Natur.402..672L.
- "Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network". EMBO Reports 2 (4): 330–5. April 2001. doi:10.1093/embo-reports/kve061. PMID 11306555.
- "Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function". Cancer Research 61 (8): 3443–9. April 2001. PMID 11309306.
- "Use of chromatin immunoprecipitation to clone novel E2F target promoters". Molecular and Cellular Biology 21 (20): 6820–32. October 2001. doi:10.1128/MCB.21.20.6820-6832.2001. PMID 11564866.
- "A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice". Neuron 35 (5): 921–33. August 2002. doi:10.1016/S0896-6273(02)00861-9. PMID 12372286.
- "Genes encoding Pir51, Beclin 1, RbAp48 and aldolase b are up or down-regulated in human primary hepatocellular carcinoma". World Journal of Gastroenterology 10 (4): 509–13. February 2004. doi:10.3748/wjg.v10.i4.509. PMID 14966907.
- "Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1". The Journal of Biological Chemistry 279 (18): 18384–91. April 2004. doi:10.1074/jbc.M313561200. PMID 14970205.
- "Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity". Experimental Cell Research 307 (1): 26–40. July 2005. doi:10.1016/j.yexcr.2005.02.023. PMID 15922724.
- "Characterization of an ERAD gene as VPS30/ATG6 reveals two alternative and functionally distinct protein quality control pathways: one for soluble Z variant of human alpha-1 proteinase inhibitor (A1PiZ) and another for aggregates of A1PiZ". Molecular Biology of the Cell 17 (1): 203–12. January 2006. doi:10.1091/mbc.E04-09-0779. PMID 16267277.
- "Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking". Journal of Cell Science 119 (Pt 2): 259–70. January 2006. doi:10.1242/jcs.02735. PMID 16390869.
- "Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1". The Journal of Biological Chemistry 281 (20): 14474–85. May 2006. doi:10.1074/jbc.M600364200. PMID 16522639.
- "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14. May 2006. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
- "Partial Beclin 1 silencing aggravates doxorubicin- and Fas-induced apoptosis in HepG2 cells". World Journal of Gastroenterology 12 (18): 2895–900. May 2006. doi:10.3748/wjg.v12.i18.2895. PMID 16718815.
External links
- Human BECN1 genome location and BECN1 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: Q14457 (Beclin-1) at the PDBe-KB.
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