BECN1
From Wikipedia, the free encyclopedia
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 (Atg) 6 and BEC-1 in the C. elegans nematode.[3]
Beclin-1 participates in the regulation of autophagy and has an important role in development, tumorigenesis, and neurodegeneration.[4] Beclin-1 and its binding partner class III phosphoinositide 3-kinase (PI3K), also named Vps34, are required for the initiation of the formation of the autophagosome in autophagy.
Role in disease
Schizophrenia is associated with low levels of Beclin-1 in the hippocampus of the affected which causes diminished autophagy which in turn results in increased neuronal cell death.[5]
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.[8]
References
- ↑ 1.0 1.1 Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, Herman B, Levine B (Nov 1998). "Protection against Fatal Sindbis Virus Encephalitis by Beclin, a Novel Bcl-2-Interacting Protein". J Virol 72 (11): 8586–96. 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, Kovacs AL, Müller F (August 2005). "Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans". Curr. Biol. 15 (16): 1513–7. doi:10.1016/j.cub.2005.07.035. PMID 16111945.
- ↑ Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, Heintz N, Yue Z (April 2009). "Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex". Nat. Cell Biol. 11 (4): 468–76. doi:10.1038/ncb1854. PMC 2664389. PMID 19270693.
- ↑ Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, Dean B, Levine J, Agam G, Gozes I (December 2013). "Autophagy has a key role in the pathophysiology of schizophrenia". Mol. Psychiatry. doi:10.1038/mp.2013.174. PMID 24365867. Lay summary – MediLexicon International Ltd.
- ↑ Erlich S, Mizrachy L, Segev O, Lindenboim L, Zmira O, Adi-Harel S, Hirsch JA, Stein R, Pinkas-Kramarski R (2007). "Differential interactions between Beclin 1 and Bcl-2 family members". Autophagy 3 (6): 561–8. 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.
- ↑ Kara NZ, Toker L, Agam G, Anderson GW, Belmaker RH, Einat H. (2013). Trehalose induced antidepressant-like effects and autophagy enhancement in mice. PMID 23644913.
Further reading
- Funderburk SF, Wang QJ, Yue Z (June 2010). "The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond". Trends Cell Biol. 20 (6): 355–62. doi:10.1016/j.tcb.2010.03.002. PMID 20356743.
- Rommens JM, Durocher F, McArthur J, et al. (1996). "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 (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, et al. (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, et al. (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, et al. (2000). "Induction of autophagy and inhibition of tumorigenesis by beclin 1". Nature 402 (6762): 672–6. doi:10.1038/45257. PMID 10604474.
- Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T (2001). "Beclin–phosphatidylinositol 3-kinase complex functions at the trans-Golgi network". EMBO Rep. 2 (4): 330–5. doi:10.1093/embo-reports/kve061. PMC 1083858. PMID 11306555.
- Liang XH, Yu J, Brown K, Levine B (2001). "Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function". Cancer Res. 61 (8): 3443–9. PMID 11309306.
- Weinmann AS, Bartley SM, Zhang T, et al. (2001). "Use of Chromatin Immunoprecipitation To Clone Novel E2F Target Promoters". Mol. Cell. Biol. 21 (20): 6820–32. doi:10.1128/MCB.21.20.6820-6832.2001. PMC 99859. PMID 11564866.
- Yue Z, Horton A, Bravin M, et al. (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.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Song H, Xia SL, Liao C, et al. (2004). "Genes encoding Pir51, Beclin 1, RbAp48 and aldolase b are up or down-regulated in human primary hepatocellular carcinoma". World J. Gastroenterol. 10 (4): 509–13. PMID 14966907.
- Scarlatti F, Bauvy C, Ventruti A, et al. (2004). "Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1". J. Biol. Chem. 279 (18): 18384–91. doi:10.1074/jbc.M313561200. PMID 14970205.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Furuya D, Tsuji N, Yagihashi A, Watanabe N (2005). "Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity". Exp. Cell Res. 307 (1): 26–40. doi:10.1016/j.yexcr.2005.02.023. PMID 15922724.
- Kruse KB, Brodsky JL, McCracken AA (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 α-1 Proteinase Inhibitor (A1PiZ) and Another for Aggregates of A1PiZ". Mol. Biol. Cell 17 (1): 203–12. doi:10.1091/mbc.E04-09-0779. PMC 1345659. PMID 16267277.
- Zeng X, Overmeyer JH, Maltese WA (2006). "Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking". J. Cell. Sci. 119 (Pt 2): 259–70. doi:10.1242/jcs.02735. PMID 16390869.
- Shibata M, Lu T, Furuya T, et al. (2006). "Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1". J. Biol. Chem. 281 (20): 14474–85. doi:10.1074/jbc.M600364200. PMID 16522639.
- Lim J, Hao T, Shaw C, et al. (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.
- Daniel F, Legrand A, Pessayre D, et al. (2006). "Partial Beclin 1 silencing aggravates doxorubicin- and Fas-induced apoptosis in HepG2 cells". World J. Gastroenterol. 12 (18): 2895–900. PMID 16718815.
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