Beclin_1

BECN1

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] 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.

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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. [1]
    GRCh38: Ensembl release 89: ENSG00000126581 – Ensembl, May 2017
  2. [2]
    GRCm38: Ensembl release 89: ENSMUSG00000035086 – Ensembl, May 2017
  3. [3]
    "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. [4]
    "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. [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. [6]
    "Entrez Gene: BECN1 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)".
  7. [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. Bibcode:2005CBio...15.1513T. doi:10.1016/j.cub.2005.07.035. PMID 16111945. S2CID 7404414.
  8. [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. [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. [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. [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. [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. [13]
    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.
  14. [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.

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