BECN1
Protein-coding gene in the species Homo sapiens
Beclin-1 is a protein that in humans is encoded by the BECN1 gene .[ 5] [ 6] ortholog of the yeast autophagy-related gene 6 (Atg6) and BEC-1 in the C. elegans nematode .[ 7] 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 .[ 8] Ovarian cancer with upregulated autophagy has a less aggressive behavior and is more responsive to chemotherapy.[ 9]
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.[ 10]
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.[ 14]
References
^ a b c GRCh38: Ensembl release 89: ENSG00000126581 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035086 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ a b Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, et al. (November 1998). "Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein" . Journal of Virology . 72 (11): 8586–96. doi :10.1128/JVI.72.11.8586-8596.1998 . PMC 110269 PMID 9765397 . ^ "Entrez Gene: BECN1 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)" .^ Takacs-Vellai K, Vellai T, Puoti A, Passannante M, Wicky C, Streit A, et al. (August 2005). "Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans" . Current Biology . 15 (16): 1513–7. Bibcode :2005CBio...15.1513T . doi :10.1016/j.cub.2005.07.035 PMID 16111945 . S2CID 7404414 . ^ Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, et al. (April 2009). "Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex" . Nature Cell Biology . 11 (4): 468–76. doi :10.1038/ncb1854 . PMC 2664389 PMID 19270693 . ^ a b Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, et al. (2014). "Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer" . BioMed Research International . 2014 : 462658. doi :10.1155/2014/462658 PMC 4127242 PMID 25136588 . ^ Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, et al. (February 2015). "Autophagy has a key role in the pathophysiology of schizophrenia" . Molecular Psychiatry . 20 (1): 126–32. doi :10.1038/mp.2013.174 . PMC 4320293 PMID 24365867 . Whiteman H (January 1, 2014). "New molecular discovery provides clues to cause of schizophrenia" . MediLexicon International Ltd . ^ Erlich S, Mizrachy L, Segev O, Lindenboim L, Zmira O, Adi-Harel S, et al. (2007). "Differential interactions between Beclin 1 and Bcl-2 family members" . Autophagy . 3 (6): 561–8. doi :10.4161/auto.4713 PMID 17643073 . ^ Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N (August 2002). "A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice" . Neuron . 35 (5): 921–33. doi :10.1016/S0896-6273(02)00861-9 PMID 12372286 . S2CID 10534933 . ^ a b Chang C, Young LN, Morris KL, von Bülow S, Schöneberg J, Yamamoto-Imoto H, 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 . PMC 6450660 PMID 30581147 . ^ Kara NZ, Toker L, Agam G, Anderson GW, Belmaker RH, Einat H (September 2013). "Trehalose induced antidepressant-like effects and autophagy enhancement in mice". Psychopharmacology . 229 (2): 367–75. doi :10.1007/s00213-013-3119-4 . PMID 23644913 . S2CID 17641899 .
Further reading
Funderburk SF, Wang QJ, Yue Z (June 2010). "The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond" . Trends in Cell Biology . 20 (6): 355–62. doi :10.1016/j.tcb.2010.03.002 . PMC 3781210 PMID 20356743 . Rommens JM, Durocher F, McArthur J, Tonin P, LeBlanc JF, Allen T, et al. (August 1995). "Generation of a transcription map at the HSD17B locus centromeric to BRCA1 at 17q21". Genomics . 28 (3): 530–42. doi :10.1006/geno.1995.1185 . PMID 7490091 . Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene . 138 (1–2): 171–4. doi :10.1016/0378-1119(94)90802-8 . PMID 8125298 . Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene . 200 (1–2): 149–56. doi :10.1016/S0378-1119(97)00411-3 . PMID 9373149 . Aita VM, Liang XH, Murty VV, Pincus DL, Yu W, Cayanis E, et al. (July 1999). "Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21" . Genomics . 59 (1): 59–65. doi :10.1006/geno.1999.5851 PMID 10395800 . Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. (December 1999). "Induction of autophagy and inhibition of tumorigenesis by beclin 1". Nature . 402 (6762): 672–6. Bibcode :1999Natur.402..672L . doi :10.1038/45257 . PMID 10604474 . S2CID 4423132 . Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T (April 2001). "Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network" . EMBO Reports . 2 (4): 330–5. doi :10.1093/embo-reports/kve061 . PMC 1083858 PMID 11306555 . Liang XH, Yu J, Brown K, Levine B (April 2001). "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. PMID 11309306 . Weinmann AS, Bartley SM, Zhang T, Zhang MQ, Farnham PJ (October 2001). "Use of chromatin immunoprecipitation to clone novel E2F target promoters" . Molecular and Cellular Biology . 21 (20): 6820–32. doi :10.1128/MCB.21.20.6820-6832.2001 . PMC 99859 PMID 11564866 . Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N (August 2002). "A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice" . Neuron . 35 (5): 921–33. doi :10.1016/S0896-6273(02)00861-9 PMID 12372286 . S2CID 10534933 . Song H, Xia SL, Liao C, Li YL, Wang YF, Li TP, et al. (February 2004). "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. doi :10.3748/wjg.v10.i4.509 PMC 4716970 PMID 14966907 . Scarlatti F, Bauvy C, Ventruti A, Sala G, Cluzeaud F, Vandewalle A, et al. (April 2004). "Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1" . The Journal of Biological Chemistry . 279 (18): 18384–91. doi :10.1074/jbc.M313561200 PMID 14970205 . Furuya D, Tsuji N, Yagihashi A, Watanabe N (July 2005). "Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity". Experimental Cell Research . 307 (1): 26–40. doi :10.1016/j.yexcr.2005.02.023 . PMID 15922724 . Kruse KB, Brodsky JL, McCracken AA (January 2006). "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. doi :10.1091/mbc.E04-09-0779 . PMC 1345659 PMID 16267277 . Zeng X, Overmeyer JH, Maltese WA (January 2006). "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. doi :10.1242/jcs.02735 PMID 16390869 . Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, et al. (May 2006). "Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1" . The Journal of Biological Chemistry . 281 (20): 14474–85. doi :10.1074/jbc.M600364200 PMID 16522639 . Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, et al. (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration" . Cell . 125 (4): 801–14. doi :10.1016/j.cell.2006.03.032 PMID 16713569 . S2CID 13709685 . Daniel F, Legrand A, Pessayre D, Vadrot N, Descatoire V, Bernuau D (May 2006). "Partial Beclin 1 silencing aggravates doxorubicin- and Fas-induced apoptosis in HepG2 cells" . World Journal of Gastroenterology . 12 (18): 2895–900. doi :10.3748/wjg.v12.i18.2895 PMC 4087807 PMID 16718815 .
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