BECN1 Target Analysis Report Summary
About the Target
Beclin-1, also known as BECN1, plays a crucial role in the regulation of autophagy, a cellular process involved in the recycling of nutrients and the degradation of cellular components. Autophagosome assembly involves several steps, including the transformation from the pre-autophagosomal structure to phagophore and autophagosomes, followed by fusion with lysosomes for degradation [1]. The phosphorylation of Beclin-1 is a critical regulatory event that impacts autophagy. Various protein complexes and phosphorylation events are involved in the modulation of Beclin-1 function [1].
Autophagy is regulated by multiple pathways, with mTOR being one of the key regulators. mTORC1, along with other pathways such as cAMP, LKB, AMPK, and PKA, converge to regulate autophagy. AMPK inhibits mTORC1 through direct interaction or by activating the TSC2 protein. The p70S6K protein, a substrate of mTORC1, positively regulates autophagy [2].
In the context of potyviral infection, Beclin-1 has been found to interact with the viral RNA-dependent RNA polymerase (RdRp) and inhibit virus replication. Beclin-1 can also act as a cargo receptor, guiding the viral replication complex to autophagosomes for degradation. Additionally, the potyviral virulence factor HC-Pro and VPg are both targeted for degradation by the autophagy pathway. The role of autophagy in potyviral infection is still under investigation [3].
The interaction between Beclin-1 and Bcl-2/XL is regulated by phosphorylation events. Mst1 phosphorylates Beclin-1 at Thr108, promoting the binding of Beclin-1 to Bcl-2/XL, which inhibits autophagosome formation. Conversely, phosphorylation of Beclin-1 at Thr119 by DAPK or ROCK1 promotes the dissociation of Beclin-1 from Bcl-2/XL. Phosphorylation of Bcl-2/XL at Thr69, Ser79, and Ser87 also facilitates the dissociation of Beclin-1 from Bcl-2/XL. Additionally, phosphorylation events involving MK2/MK3, ULK1, and AMPK promote the formation of the Beclin-1-Atg14L heterodimer, leading to the activation of Vps34 kinase and the stimulation of autophagosome formation [4].
In a study involving PHGDH knockdown, it was observed that the upregulation of autophagy was mediated by p-AMPK through the phosphorylation of Beclin-1. PHGDH knockdown led to an increase in p-AMPK levels, without a concurrent increase in p-TSC2 levels. This upregulation of autophagy was found to be partially dependent on Beclin-1 activation, suggesting that PHGDH inhibition promotes autophagy through Beclin-1-mediated induction of canonical autophagy [5].
In summary, Beclin-1 is a key regulator of autophagy, involved in various processes and interactions. Its phosphorylation and interaction with proteins like Bcl-2/XL play a crucial role in autophagosome formation and function. Additionally, Beclin-1 has been implicated in the regulation of autophagy in the context of potyviral infection and through the modulation of energy depletion pathways. Further research is needed to fully understand the mechanisms and implications of Beclin-1 in autophagy regulation.
Beclin-1, also known as BECN1, is a protein that plays a role in various processes in cancer development and treatment. It has been shown that Beclin-1 can inhibit tumor initiation in transgenic mice, and its deletions are common in human cancers [7]. In HCT116 xenograft tumors, Beclin-1 expression is increased upon irradiation treatment, and its reduction through siRNA delivery leads to a decrease in tumor volume and weight [6]. Additionally, Beclin-1 is associated with the inhibition of MMP-9 and VEGF to prevent tumor angiogenesis and cancer cell metastasis [7].
However, the role of Beclin-1 in cancer is controversial. It has been observed that autophagy, induced by Beclin-1, can both suppress tumor initiation and support the maintenance of established tumors during hypoxia, thereby promoting tumor invasion and metastasis [7]. Furthermore, the interruption of signaling transmission from Ras to c-Raf in certain cells can impede the effectiveness of salirasib, a drug being studied for cancer treatment [8].
In terms of therapeutic implications, Beclin-1 holds potential as a target for novel cancer stem cell (CSC) therapeutics, although further investigation is required in this area [7]. Additionally, a designed peptide targeting the Beclin-1 coiled-coil domain has been shown to enhance autophagy and endolysosomal trafficking, suggesting a potential strategy for modulating Beclin-1 activity [9].
Overall, Beclin-1 plays a complex role in cancer, with its involvement in autophagy influencing tumor initiation, maintenance, invasion, and metastasis. Its expression and modulation hold promise for understanding and developing new approaches for cancer treatment.
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ABCB1 | ABCG2 | ACE2 | AHR | AKT1 | ALK | AR | ATM | BAX | BCL2 | BCL2L1 | BECN1 | BRAF | BRCA1 | CAMP | CASP3 | CASP9 | CCL5 | CCND1 | CD274 | CD4 | CD8A | CDH1 | CDKN1A | CDKN2A | CREB1 | CXCL8 | CXCR4 | DNMT1 | EGF | EGFR | EP300 | ERBB2 | EREG | ESR1 | EZH2 | FN1 | FOXO3 | HDAC9 | HGF | HMGB1 | HSP90AA1 | HSPA4 | HSPA5 | IDO1 | IFNA1 | IGF1 | IGF1R | IL17A | IL6 | INS | JUN | KRAS | MAPK1 | MAPK14 | MAPK3 | MAPK8 | MAPT | MCL1 | MDM2 | MET | MMP9 | MTOR | MYC | NFE2L2 | NLRP3 | NOTCH1 | PARP1 | PCNA | PDCD1 | PLK1 | PRKAA1 | PRKAA2 | PTEN | PTGS2 | PTK2 | RELA | SIRT1 | SLTM | SMAD4 | SOD1 | SQSTM1 | SRC | STAT1 | STAT3 | STAT5A | TAK1 | TERT | TLR4 | TNF | TP53 | TXN | VEGFA | YAP1
