Molecule Information

General Information of the Molecule (ID: Mol04404)

• Name: Beclin-1 (BECN1) ,Homo sapiens
• Synonyms: Coiled-coil myosin-like BCL2-interacting protein; Protein GT197
• Molecule Type: Protein
• Gene Name: BECN1
• Gene ID: 8678
• Sequence:
  MEGSKTSNNSTMQVSFVCQRCSQPLKLDTSFKILDRVTIQELTAPLLTTAQAKPGETQEE
  ETNSGEEPFIETPRQDGVSRRFIPPARMMSTESANSFTLIGEASDGGTMENLSRRLKVT
  G DLFDIMSGQTDVDHPLCEECTDTLLDQLDTQLNVTENECQNYKRCLEILEQMNEDDSE
  QL QMELKELALEEERLIQELEDVEKNRKIVAENLEKVQAEAERLDQEEAQYQREYSEFK
  RQQ LELDDELKSVENQMRYAQTQLDKLKKTNVFNATFHIWHSGQFGTINNFRLGRLPSV
  PVEW NEINAAWGQTVLLLHALANKMGLKFQRYRLVPYGNHSYLESLTDKSKELPLYCSG
  GLRFF WDNKFDHAMVAFLDCVQQFKEEVEKGETRFCLPYRMDVEKGKIEDTGGSGGSYS
  IKTQFN SEEQWTKALKFMLTNLKWGLAWVSSQFYNK
• Function: Plays a central role in autophagy . Acts as a core subunit of the PI3Kcomplex that mediates formation of phosphatidylinositol 3-phosphate;different complex forms are believed to play a role in multiplemembrane trafficking pathways: PI3KC3-C1 is involved in initiation ofautophagosomes and PI3KC3-C2 in maturation of autophagosomes andendocytosis. Involved in regulation of degradative endocytictrafficking and required for the abscission step in cytokinesis,probably in the context of PI3KC3-C2 . Essential for the formation ofPI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis. May play a role in antiviral host defense.{ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20208530,ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:21358617,ECO:0000269|PubMed:23184933, ECO:0000269|PubMed:23974797,ECO:0000269|PubMed:25275521, ECO:0000269|PubMed:25484083,ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:28445460,ECO:0000269|PubMed:37776275, ECO:0000269|PubMed:9765397}.; Beclin-1-C 35 kDa localized to mitochondria can promoteapoptosis; it induces the mitochondrial translocation of BAX and therelease of proapoptotic factors. {ECO:0000269|PubMed:21364619,ECO:0000269|PubMed:26263979}.; Protects against infection by aneurovirulent strain of Sindbis virus. {ECO:0000269|PubMed:9765397}.
• Uniprot ID: BECN1_HUMAN
• Ensembl ID: ENSG0000012658113
• HGNC ID: HGNC:1034

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Idebenone

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Diabetic retinopathy [ICD-11: 9B71.0] [1]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Sensitive Drug: Idebenone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Akt signaling pathway; Regulation; N.A.
• In Vitro Model: RF/6A cells; Chorioretinal; Homo sapiens (Human); CVCL_4552
• In Vivo Model: Diabetic rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Ocular fundus ultrasound testing; Histological assay; Cell proliferation assay
• Mechanism Description: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.The PI3K/Akt/mTOR signaling pathway acts as the mediator of IDE in alleviating DR.IDE treatment suppressed the activation of the PI3K/Akt/mTOR signaling pathway, and PI3K signaling repressed the protective role of IDE in DR, explaining the IDE-suppressed autophagy in DR.

Investigative Drug(s) 1 drug(s) in total

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [2]

• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: beta2AR-Akt feedback loop signalling pathway; Regulation; N.A.
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: Colony formation assay; Stem cell sphere formation assay
• Mechanism Description: In this study, we found that NNK promoted stemness and gemcitabine resistance in pancreatic cancer cell lines. Moreover, NNK increased autophagy and elevated the expression levels of the autophagy-related markers autophagy-related gene 5 (ATG5), autophagy-related gene 7 (ATG7), and Beclin1. Furthermore, the results showed that NNK-promoted stemness and gemcitabine resistance was partially dependent on the role of NNK in cell autophagy, which is mediated by the beta2-adrenergic receptor (beta2AR)-Akt axis. Finally, we proved that NNK intervention could not only activate beta2AR, but also increase its expression, making beta2AR and Akt form a feedback loop. Overall, these findings show that the NNK-induced beta2AR-Akt feedback loop promotes stemness and gemcitabine resistance in pancreatic cancer cells.

References

• Ref 1: Idebenone Attenuates Diabetic Retinopathy by Modulating Autophagy Via Targeting Akt Signaling. Curr Med Chem. 2024 Nov 1.
• Ref 2: NNK from tobacco smoking enhances pancreatic cancer cell stemness and chemoresistance by creating a beta2AR-Akt feedback loop that activates autophagy. Mol Oncol. 2022 Aug;16(15):2881-2895.