BECN1

BECN1
Estruturas disponíveis
PDB	Pesquisa Human UniProt: K7ER46 PDBe K7ER46 RCSB
Lista de códigos id do PDB
	2P1L, 2PON, 3DVU, 4DDP, 4MI8
Identificadores
Nomes alternativos	BECN1
IDs externos	OMIM: 604378 HomoloGene: 2794 GeneCards: BECN1
Ontologia genética
Função molecular	• phosphatidylinositol 3-kinase binding; • GO:0001948, GO:0016582 ligação a proteínas plasmáticas; • GTPase binding; • ubiquitin protein ligase binding; • protein kinase binding; • protein homodimerization activity;
Componente celular	• endosome membrane; • citoplasma; • mitochondrial membranes; • trans-Golgi network; • complexo de Golgi; • citosol; • núcleo celular; • autofagossoma; • phagophore assembly site; • membrane; • dendrito; • retículo endoplasmático; • phosphatidylinositol 3-kinase complex, class III; • endoplasmic reticulum membrane; • phosphatidylinositol 3-kinase complex, class III, type II; • GO:0016023 cytoplasmic vesicle; • endossoma; • extrinsic component of membrane; • phosphatidylinositol 3-kinase complex, class III, type I; • phagocytic vesicle; • mitocôndria; • GO:0009327 complexo macromolecular;
Processo biológico	• negative regulation of cell population proliferation; • response to hypoxia; • cellular response to aluminum ion; • response to vitamin E; • lysosome organization; • ciclo celular; • positive regulation of phosphatidylinositol 3-kinase signaling; • cellular response to glucose starvation; • cellular defense response; • citocinese; • cellular response to epidermal growth factor stimulus; • divisão celular; • receptor catabolic process; • autophagy of nucleus; • cellular response to nitrogen starvation; • GO:0022415 viral process; • late endosome to vacuole transport; • GO:0097285 apoptose; • cytoplasm to vacuole transport by the Cvt pathway; • endocitose; • engulfment of apoptotic cell; • positive regulation of attachment of mitotic spindle microtubules to kinetochore; • amyloid-beta metabolic process; • neuron development; • resposta antiviral; • response to other organism; • mitotic metaphase plate congression; • GO:0048552 regulation of catalytic activity; • negative regulation of reactive oxygen species metabolic process; • regulation of cytokinesis; • negative regulation of apoptotic process; • negative regulation of cell death; • autophagosome assembly; • macroautophagy; • GO:0010260 envelhecimento; • response to iron(II) ion; • response to lead ion; • protein deubiquitination; • response to nutrient levels; • cellular response to amino acid starvation; • cellular response to hydrogen peroxide; • cellular response to copper ion; • negative regulation of lysosome organization; • positive regulation of autophagosome assembly; • Mitofagia; • mitophagy; • autofagia; • positive regulation of autophagy; • response to mitochondrial depolarisation; • early endosome to late endosome transport; • negative regulation of autophagy; • positive regulation of cardiac muscle hypertrophy; • negative regulation of autophagosome assembly; • positive regulation of intrinsic apoptotic signaling pathway;
	Sources:Amigo / QuickGO
Padrão de expressão RNA
	; ;
	Mais dados de referência de expressão
Ortólogos
	8678
	n/a
	ENSG00000126581
	n/a
	Q14457
	n/a
	NM_001313998; NM_001313999; NM_001314000; NM_003766
	n/a
	NP_001300927; NP_001300928; NP_001300929; NP_003757
	n/a
	Wikidata
Ver/Editar Humano

Beclina-1 é uma proteína que, em humanos, é codificada pelo gene BECN1. A beclina-1 é um ortólogo em mamíferos do gene 6 relacionado à autofagia (Atg6) de levedura e BEC-1 no nematoide Caenorhabditis elegans. Esta proteína interage com o BCL-2 ou com a PI3k classe III, desempenhando um papel crítico na regulação tanto da autofagia quanto da morte celular.

Papel na doença

A beclina-1 desempenha um papel importante na tumorigênese e na neurodegeneração, estando implicada na morte celular programada autofágica. O câncer de ovário com autofagia regulada positivamente tem um comportamento menos agressivo e é mais responsivo à quimioterapia.

A esquizofrenia está associada a baixos níveis de beclina-1 no hipocampo dos afetados, o que causa diminuição da autofagia, que, por sua vez, resulta em aumento da morte das células neuronais.

Interações

Demonstrou-se que a BECN1 interage com:

Moduladores

Trealose

A trealose reduz a proporção p62/Beclina-1 e aumenta a autofagia no córtex frontal de camundongos ICR, possivelmente pelo aumento da Beclina-1.

Referências

↑ «Human PubMed Reference:»
1 2 Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, Herman B, Levine B (Novembro de 1998). «Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein». Journal of Virology. 72 (11): 8586–96. PMC 110269. PMID 9765397. doi:10.1128/JVI.72.11.8586-8596.1998
↑ «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 (Agosto de 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. PMID 16111945. doi:10.1016/j.cub.2005.07.035
↑ Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, Heintz N, Yue Z (Abril de 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. PMC 2664389. PMID 19270693. doi:10.1038/ncb1854
1 2 Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, Alabiso O, Arisio R, Katsaros D, Benedetto C, Isidoro C (2014). «Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer». BioMed Research International. 2014. PMC 4127242. PMID 25136588. doi:10.1155/2014/462658
↑ Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, Dean B, Levine J, Agam G, Gozes I (Fevereiro de 2015). «Autophagy has a key role in the pathophysiology of schizophrenia». Molecular Psychiatry. 20 (1): 126–32. PMC 4320293. PMID 24365867. doi:10.1038/mp.2013.174 *
↑ 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. doi:10.4161/auto.4713
↑ Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N (Agosto de 2002). «A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice». Neuron. 35 (5): 921–33. PMID 12372286. doi:10.1016/S0896-6273(02)00861-9
1 2 Chang, Chunmei; Young, Lindsey N.; Morris, Kyle L.; von Bülow, Sören; Schöneberg, Johannes; Yamamoto-Imoto, Hitomi; Oe, Yukako; Yamamoto, Kentaro; Nakamura, Shuhei; Stjepanovic, Goran; Hummer, Gerhard (17 de Janeiro de 2019). «Bidirectional Control of Autophagy by BECN1 BARA Domain Dynamics». Molecular Cell. 73 (2): 339–353.e6. ISSN 1097-4164. PMC 6450660. PMID 30581147. doi:10.1016/j.molcel.2018.10.035
↑ Kara NZ, Toker L, Agam G, Anderson GW, Belmaker RH, Einat H (Setembro de 2013). «Trehalose induced antidepressant-like effects and autophagy enhancement in mice». Psychopharmacology. 229 (2): 367–75. PMID 23644913. doi:10.1007/s00213-013-3119-4

Leitura adicional

Funderburk SF, Wang QJ, Yue Z (Junho de 2010). «The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond». Trends in Cell Biology. 20 (6): 355–62. PMC 3781210. PMID 20356743. doi:10.1016/j.tcb.2010.03.002
Rommens JM, Durocher F, McArthur J, Tonin P, LeBlanc JF, Allen T, Samson C, Ferri L, Narod S, Morgan K (Agosto de 1995). «Generation of a transcription map at the HSD17B locus centromeric to BRCA1 at 17q21». Genomics. 28 (3): 530–42. PMID 7490091. doi:10.1006/geno.1995.1185
Maruyama K, Sugano S (Janeiro de 1994). «Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides». Gene. 138 (1–2): 171–4. PMID 8125298. doi:10.1016/0378-1119(94)90802-8
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Outubro de 1997). «Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library». Gene. 200 (1–2): 149–56. PMID 9373149. doi:10.1016/S0378-1119(97)00411-3
Aita VM, Liang XH, Murty VV, Pincus DL, Yu W, Cayanis E, Kalachikov S, Gilliam TC, Levine B (Julho de 1999). «Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21». Genomics. 59 (1): 59–65. PMID 10395800. doi:10.1006/geno.1999.5851
Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (Dezembro de 1999). «Induction of autophagy and inhibition of tumorigenesis by beclin 1». Nature. 402 (6762): 672–6. Bibcode:1999Natur.402..672L. PMID 10604474. doi:10.1038/45257
Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T (Abril de 2001). «Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network». EMBO Reports. 2 (4): 330–5. PMC 1083858. PMID 11306555. doi:10.1093/embo-reports/kve061
Liang XH, Yu J, Brown K, Levine B (Abril de 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 (Outubro de 2001). «Use of chromatin immunoprecipitation to clone novel E2F target promoters». Molecular and Cellular Biology. 21 (20): 6820–32. PMC 99859. PMID 11564866. doi:10.1128/MCB.21.20.6820-6832.2001
Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N (Agosto de 2002). «A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice». Neuron. 35 (5): 921–33. PMID 12372286. doi:10.1016/S0896-6273(02)00861-9
Song H, Xia SL, Liao C, Li YL, Wang YF, Li TP, Zhao MJ (Fevereiro de 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. PMC 4716970. PMID 14966907. doi:10.3748/wjg.v10.i4.509
Scarlatti F, Bauvy C, Ventruti A, Sala G, Cluzeaud F, Vandewalle A, Ghidoni R, Codogno P (Abril de 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. PMID 14970205. doi:10.1074/jbc.M313561200
Furuya D, Tsuji N, Yagihashi A, Watanabe N (Julho de 2005). «Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity». Experimental Cell Research. 307 (1): 26–40. PMID 15922724. doi:10.1016/j.yexcr.2005.02.023
Kruse KB, Brodsky JL, McCracken AA (Janeiro de 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. PMC 1345659. PMID 16267277. doi:10.1091/mbc.E04-09-0779
Zeng X, Overmeyer JH, Maltese WA (Janeiro de 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. PMID 16390869. doi:10.1242/jcs.02735
Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, MacDonald M, Yankner B, Yuan J (Maio de 2006). «Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1». The Journal of Biological Chemistry. 281 (20): 14474–85. PMID 16522639. doi:10.1074/jbc.M600364200
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 (Maio de 2006). «A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration». Cell. 125 (4): 801–14. PMID 16713569. doi:10.1016/j.cell.2006.03.032
Daniel F, Legrand A, Pessayre D, Vadrot N, Descatoire V, Bernuau D (Maio de 2006). «Partial Beclin 1 silencing aggravates doxorubicin- and Fas-induced apoptosis in HepG2 cells». World Journal of Gastroenterology. 12 (18): 2895–900. PMC 4087807. PMID 16718815. doi:10.3748/wjg.v12.i18.2895

Ligações externas

Localização do genoma humano BECN1 e página de detalhes do gene BECN1 no UCSC Genome Browser.
Visão geral de todas as informações estruturais disponíveis no PDB para UniProt: Q14457 (Beclin-1) no PDBe-KB.

[1] «Human PubMed Reference:»

[pmid9765397-2] 1 2 Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, Herman B, Levine B (Novembro de 1998). «Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein». Journal of Virology. 72 (11): 8586–96. PMC 110269. PMID 9765397. doi:10.1128/JVI.72.11.8586-8596.1998

[entrez-3] «Entrez Gene: BECN1 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)»

[pmid16111945-4] Takacs-Vellai K, Vellai T, Puoti A, Passannante M, Wicky C, Streit A, Kovacs AL, Müller F (Agosto de 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. PMID 16111945. doi:10.1016/j.cub.2005.07.035

[pmid19270693-5] Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, Heintz N, Yue Z (Abril de 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. PMC 2664389. PMID 19270693. doi:10.1038/ncb1854

[Valente_2014-6] 1 2 Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, Alabiso O, Arisio R, Katsaros D, Benedetto C, Isidoro C (2014). «Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer». BioMed Research International. 2014. PMC 4127242. PMID 25136588. doi:10.1155/2014/462658

[pmid24365867-7] Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, Dean B, Levine J, Agam G, Gozes I (Fevereiro de 2015). «Autophagy has a key role in the pathophysiology of schizophrenia». Molecular Psychiatry. 20 (1): 126–32. PMC 4320293. PMID 24365867. doi:10.1038/mp.2013.174 *

[pmid17643073-8] 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. doi:10.4161/auto.4713

[pmid12372286-9] Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N (Agosto de 2002). «A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice». Neuron. 35 (5): 921–33. PMID 12372286. doi:10.1016/S0896-6273(02)00861-9

[:0-10] 1 2 Chang, Chunmei; Young, Lindsey N.; Morris, Kyle L.; von Bülow, Sören; Schöneberg, Johannes; Yamamoto-Imoto, Hitomi; Oe, Yukako; Yamamoto, Kentaro; Nakamura, Shuhei; Stjepanovic, Goran; Hummer, Gerhard (17 de Janeiro de 2019). «Bidirectional Control of Autophagy by BECN1 BARA Domain Dynamics». Molecular Cell. 73 (2): 339–353.e6. ISSN 1097-4164. PMC 6450660. PMID 30581147. doi:10.1016/j.molcel.2018.10.035

[11] Kara NZ, Toker L, Agam G, Anderson GW, Belmaker RH, Einat H (Setembro de 2013). «Trehalose induced antidepressant-like effects and autophagy enhancement in mice». Psychopharmacology. 229 (2): 367–75. PMID 23644913. doi:10.1007/s00213-013-3119-4