View source for BECN1

{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{Infobox_gene}}
'''Beclin-1''' is a [[protein]] that in humans is encoded by the ''BECN1'' [[gene]].<ref name="pmid9765397">{{cite journal | vauthors = Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, Herman B, Levine B | title = Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein | journal = Journal of Virology | volume = 72 | issue = 11 | pages = 8586–96 | date = November 1998 | pmid = 9765397 | pmc = 110269 | doi =  10.1128/JVI.72.11.8586-8596.1998}}</ref><ref name="entrez">{{cite web | title = Entrez Gene: BECN1 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8678}}</ref> Beclin-1 is a mammalian  [[Homology (biology)#Orthology|ortholog]] of the yeast autophagy-related gene 6 (Atg6)&nbsp; and BEC-1 in the [[Caenorhabditis elegans|C. elegans]] [[nematode]].<ref name="pmid16111945">{{cite journal | vauthors = Takacs-Vellai K, Vellai T, Puoti A, Passannante M, Wicky C, Streit A, Kovacs AL, Müller F | title = Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans | journal = Current Biology | volume = 15 | issue = 16 | pages = 1513–7 | date = August 2005 | pmid = 16111945 | doi = 10.1016/j.cub.2005.07.035 | s2cid = 7404414 | doi-access = free | bibcode = 2005CBio...15.1513T }}</ref> This protein interacts with either [[Bcl-2|BCL-2]] or [[Phosphoinositide 3-kinase|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 [[Carcinogenesis|tumorigenesis]], and [[neurodegeneration]], being implicated in the [[Autophagy|autophagic]] [[programmed cell death]].<ref name="pmid19270693">{{cite journal | vauthors = Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, Heintz N, Yue Z | title = Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex | journal = Nature Cell Biology | volume = 11 | issue = 4 | pages = 468–76 | date = April 2009 | pmid = 19270693 | pmc = 2664389 | doi = 10.1038/ncb1854 }}</ref> [[Ovarian cancer]] with upregulated [[autophagy]] has a less aggressive behavior and is more responsive to chemotherapy.<ref name="Valente_2014">{{cite journal | vauthors = Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, Alabiso O, Arisio R, Katsaros D, Benedetto C, Isidoro C | title = Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer | journal = BioMed Research International | volume = 2014 | pages = 462658 | year = 2014 | pmid = 25136588 | pmc = 4127242 | doi = 10.1155/2014/462658 | doi-access = free }}</ref>
[[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.<ref name="pmid24365867">{{cite journal | vauthors = Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, Dean B, Levine J, Agam G, Gozes I | title = Autophagy has a key role in the pathophysiology of schizophrenia | journal = Molecular Psychiatry | volume = 20 | issue = 1 | pages = 126–32 | date = February 2015 | pmid = 24365867 | pmc = 4320293 | doi = 10.1038/mp.2013.174 }}*{{lay source |template=cite web|vauthors = Whiteman H |url = http://www.medicalnewstoday.com/articles/270725.php |title = New molecular discovery provides clues to cause of schizophrenia|date = January 1, 2014 |website = MediLexicon International Ltd }}</ref>
== Interactions ==
BECN1 has been shown to [[Protein-protein interaction|interact]] with:
* [[Bcl-2]]<ref name="pmid9765397" />
* [[BCL2L2]]<ref name="pmid17643073">{{cite journal | vauthors = Erlich S, Mizrachy L, Segev O, Lindenboim L, Zmira O, Adi-Harel S, Hirsch JA, Stein R, Pinkas-Kramarski R | title = Differential interactions between Beclin 1 and Bcl-2 family members | journal = Autophagy | volume = 3 | issue = 6 | pages = 561–8 | year = 2007 | pmid = 17643073 | doi = 10.4161/auto.4713 | doi-access = free }}</ref>
* [[GOPC]]<ref name="pmid12372286">{{cite journal | vauthors = Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N | title = A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice | journal = Neuron | volume = 35 | issue = 5 | pages = 921–33 | date = August 2002 | pmid = 12372286 | doi = 10.1016/S0896-6273(02)00861-9 | s2cid = 10534933 | doi-access = free }}</ref>
* [[MAP1LC3A]]<ref name="Valente_2014" />
* [[Rubicon (protein)|Rubicon]]<ref name=":0">{{Cite journal |last1=Chang |first1=Chunmei |last2=Young |first2=Lindsey N. |last3=Morris |first3=Kyle L. |last4=von Bülow |first4=Sören |last5=Schöneberg |first5=Johannes |last6=Yamamoto-Imoto |first6=Hitomi |last7=Oe |first7=Yukako |last8=Yamamoto |first8=Kentaro |last9=Nakamura |first9=Shuhei |last10=Stjepanovic |first10=Goran |last11=Hummer |first11=Gerhard |date=2019-01-17 |title=Bidirectional Control of Autophagy by BECN1 BARA Domain Dynamics |journal=Molecular Cell |volume=73 |issue=2 |pages=339–353.e6 |doi=10.1016/j.molcel.2018.10.035 |issn=1097-4164 |pmc=6450660 |pmid=30581147}}</ref>
* [[UVRAG]]<ref name=":0" />
== Modulators ==
;Trehalose: [[Trehalose]] reduces p62/Beclin-1 ratio and increases [[autophagy]] in the frontal cortex of ICR mice, possibly by increasing Beclin-1.<ref>{{cite journal | vauthors = Kara NZ, Toker L, Agam G, Anderson GW, Belmaker RH, Einat H | title = Trehalose induced antidepressant-like effects and autophagy enhancement in mice | journal = Psychopharmacology | volume = 229 | issue = 2 | pages = 367–75 | date = September 2013 | pmid = 23644913 | doi = 10.1007/s00213-013-3119-4 | s2cid = 17641899 }}</ref>
== References ==
{{reflist}}
== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Funderburk SF, Wang QJ, Yue Z | title = The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond | journal = Trends in Cell Biology | volume = 20 | issue = 6 | pages = 355–62 | date = June 2010 | pmid = 20356743 | pmc = 3781210 | doi = 10.1016/j.tcb.2010.03.002 }}
* {{cite journal | vauthors = Rommens JM, Durocher F, McArthur J, Tonin P, LeBlanc JF, Allen T, Samson C, Ferri L, Narod S, Morgan K | title = Generation of a transcription map at the HSD17B locus centromeric to BRCA1 at 17q21 | journal = Genomics | volume = 28 | issue = 3 | pages = 530–42 | date = August 1995 | pmid = 7490091 | doi = 10.1006/geno.1995.1185 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Aita VM, Liang XH, Murty VV, Pincus DL, Yu W, Cayanis E, Kalachikov S, Gilliam TC, Levine B | title = Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21 | journal = Genomics | volume = 59 | issue = 1 | pages = 59–65 | date = July 1999 | pmid = 10395800 | doi = 10.1006/geno.1999.5851 | doi-access = free }}
* {{cite journal | vauthors = Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B | title = Induction of autophagy and inhibition of tumorigenesis by beclin 1 | journal = Nature | volume = 402 | issue = 6762 | pages = 672–6 | date = December 1999 | pmid = 10604474 | doi = 10.1038/45257 | bibcode = 1999Natur.402..672L | s2cid = 4423132 }}
* {{cite journal | vauthors = Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T | title = Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network | journal = EMBO Reports | volume = 2 | issue = 4 | pages = 330–5 | date = April 2001 | pmid = 11306555 | pmc = 1083858 | doi = 10.1093/embo-reports/kve061 }}
* {{cite journal | vauthors = Liang XH, Yu J, Brown K, Levine B | title = Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function | journal = Cancer Research | volume = 61 | issue = 8 | pages = 3443–9 | date = April 2001 | pmid = 11309306 }}
* {{cite journal | vauthors = Weinmann AS, Bartley SM, Zhang T, Zhang MQ, Farnham PJ | title = Use of chromatin immunoprecipitation to clone novel E2F target promoters | journal = Molecular and Cellular Biology | volume = 21 | issue = 20 | pages = 6820–32 | date = October 2001 | pmid = 11564866 | pmc = 99859 | doi = 10.1128/MCB.21.20.6820-6832.2001 }}
* {{cite journal | vauthors = Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N | title = A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice | journal = Neuron | volume = 35 | issue = 5 | pages = 921–33 | date = August 2002 | pmid = 12372286 | doi = 10.1016/S0896-6273(02)00861-9 | s2cid = 10534933 | doi-access = free }}
* {{cite journal | vauthors = Song H, Xia SL, Liao C, Li YL, Wang YF, Li TP, Zhao MJ | title = Genes encoding Pir51, Beclin 1, RbAp48 and aldolase b are up or down-regulated in human primary hepatocellular carcinoma | journal = World Journal of Gastroenterology | volume = 10 | issue = 4 | pages = 509–13 | date = February 2004 | pmid = 14966907 | pmc = 4716970 | doi = 10.3748/wjg.v10.i4.509 | doi-access = free }}
* {{cite journal | vauthors = Scarlatti F, Bauvy C, Ventruti A, Sala G, Cluzeaud F, Vandewalle A, Ghidoni R, Codogno P | title = Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1 | journal = The Journal of Biological Chemistry | volume = 279 | issue = 18 | pages = 18384–91 | date = April 2004 | pmid = 14970205 | doi = 10.1074/jbc.M313561200 | doi-access = free }}
* {{cite journal | vauthors = Furuya D, Tsuji N, Yagihashi A, Watanabe N | title = Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity | journal = Experimental Cell Research | volume = 307 | issue = 1 | pages = 26–40 | date = July 2005 | pmid = 15922724 | doi = 10.1016/j.yexcr.2005.02.023 }}
* {{cite journal | vauthors = Kruse KB, Brodsky JL, McCracken AA | title = 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 | journal = Molecular Biology of the Cell | volume = 17 | issue = 1 | pages = 203–12 | date = January 2006 | pmid = 16267277 | pmc = 1345659 | doi = 10.1091/mbc.E04-09-0779 }}
* {{cite journal | vauthors = Zeng X, Overmeyer JH, Maltese WA | title = Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking | journal = Journal of Cell Science | volume = 119 | issue = Pt 2 | pages = 259–70 | date = January 2006 | pmid = 16390869 | doi = 10.1242/jcs.02735 | doi-access = free }}
* {{cite journal | vauthors = Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, MacDonald M, Yankner B, Yuan J | title = Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1 | journal = The Journal of Biological Chemistry | volume = 281 | issue = 20 | pages = 14474–85 | date = May 2006 | pmid = 16522639 | doi = 10.1074/jbc.M600364200 | doi-access = free }}
* {{cite journal | vauthors = Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY | title = A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration | journal = Cell | volume = 125 | issue = 4 | pages = 801–14 | date = May 2006 | pmid = 16713569 | doi = 10.1016/j.cell.2006.03.032 | s2cid = 13709685 | doi-access = free }}
* {{cite journal | vauthors = Daniel F, Legrand A, Pessayre D, Vadrot N, Descatoire V, Bernuau D | title = Partial Beclin 1 silencing aggravates doxorubicin- and Fas-induced apoptosis in HepG2 cells | journal = World Journal of Gastroenterology | volume = 12 | issue = 18 | pages = 2895–900 | date = May 2006 | pmid = 16718815 | pmc = 4087807 | doi = 10.3748/wjg.v12.i18.2895 | doi-access = free }}
{{refend}}
== External links ==
* {{UCSC gene info|BECN1}}
* {{PDBe-KB2|Q14457|Beclin-1}}
{{PDB Gallery|geneid=8678}}
[[Category:Genes]]
[[Category:Human proteins]]