BECN1

Beclin-1 is a protein that in humans is encoded by the BECN1 gene.[5][6] Beclin-1 is a mammalian ortholog of the yeast autophagy-related gene 6 (Atg6)  and BEC-1 in the C. elegans nematode.[7] This protein interacts with either BCL-2 or PI3k class III, playing a critical role in the regulation of both autophagy and cell death.

BECN1
Available structures
PDBOrtholog search: K7ER46 PDBe K7ER46 RCSB
Identifiers
AliasesBECN1, ATG6, VPS30, beclin1, beclin 1
External IDsOMIM: 604378 MGI: 1891828 HomoloGene: 2794 GeneCards: BECN1
Orthologs
SpeciesHumanMouse
Entrez

8678

56208

Ensembl

ENSG00000126581

ENSMUSG00000035086

UniProt

Q14457

O88597

RefSeq (mRNA)

NM_001313998
NM_001313999
NM_001314000
NM_003766

NM_019584
NM_001359819
NM_001359820
NM_001359821

RefSeq (protein)

NP_001300927
NP_001300928
NP_001300929
NP_003757

NP_062530
NP_001346748
NP_001346749
NP_001346750

Location (UCSC)Chr 17: 42.81 – 42.83 MbChr 11: 101.18 – 101.19 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

  1. GRCh38: Ensembl release 89: ENSG00000126581 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000035086 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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.
  6. "Entrez Gene: BECN1 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)".
  7. 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. doi:10.1016/j.cub.2005.07.035. PMID 16111945. S2CID 7404414.
  8. 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.
  9. 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.
  10. 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.*Lay summary in: Whiteman H (January 1, 2014). "New molecular discovery provides clues to cause of schizophrenia". MediLexicon International Ltd.
  11. 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.
  12. 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.
  13. 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 (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.
  14. 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


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.