AMBRA1: A Potential Drug Target and Biomarker for Autophagy and Beclin 1 Regulation

Target Name: AMBRA1

NCBI ID: G55626

AMBRA1

AMBRA1: A Potential Drug Target and Biomarker for Autophagy and Beclin 1 Regulation

Autophagy, the process of self-cleaning by the body's cells, is a crucial regulatory process that helps maintain cellular health and longevity. Beclin 1, a transcription factor that regulates autophagy, has been implicated in various diseases, including cancer, neurodegenerative disorders, and obesity. However, the precise role of Beclin 1 in these processes remains poorly understood.

The AMBRA1 gene, which encodes a protein known as AMBRA1, has been identified as a potential drug target and biomarker for autophagy and Beclin 1 regulation. In this article, we will explore the AMBRA1 gene, its function, and its potential as a drug target.

The Function of AMBRA1

AMBRA1 is a non-coding RNA molecule that has been shown to play a critical role in regulating autophagy in various cell types. It is a key regulator of the beclin 1 gene, which encodes a transcription factor that regulates autophagy. By modulating the expression of other genes, AMBRA1 regulates the cellular response to various stimuli, including nutrients, toxins, and stress.

AMBRA1 has been shown to regulate the levels of Beclin 1 in various cell types, including neurons, macrophages, and cancer cells. It has been shown to promote Beclin 1 nuclear translocation and to enhance the transcriptional activity of Beclin 1. These effects are critical for the regulation of autophagy and the maintenance of cellular health.

The Potential of AMBRA1 as a Drug Target

The potential of AMBRA1 as a drug target is high due to its involvement in various diseases, including cancer, neurodegenerative disorders, and obesity.

AMBRA1 has been shown to be overexpressed in various types of cancer, including breast, ovarian, and prostate cancer. It has also been shown to be involved in the development of neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. Additionally, AMBRA1 has been shown to be involved in the regulation of obesity, including the development of obese rats and the increase in body mass index (BMI) in obese individuals.

Several studies have suggested that AMBRA1 may be a useful drug target for various diseases, including cancer, neurodegenerative disorders, and obesity. For example, studies have shown that inhibiting the activity of AMBRA1 may be effective in treating breast cancer, ovarian cancer, and obesity.

The Beclin 1 Involvement in AMBRA1 Regulation

The Beclin 1 gene, which encodes a transcription factor that regulates autophagy, has been shown to be regulated by AMBRA1. Beclin 1 can bind to the AMBRA1 protein and enhance its transcriptional activity. This interaction between Beclin 1 and AMBRA1 is critical for the regulation of autophagy.

The regulation of autophagy by AMBRA1 is a complex process that involves multiple interactions between various genes and molecules. One of the key interactions is the interaction between AMBRA1 and Beclin 1.

AMBRA1 Interacts with Beclin 1 to Enhance Autophagy

Several studies have shown that AMBRA1 interacts with Beclin 1 to enhance autophagy. For example, one study reported that AMBRA1 and Beclin 1 can form a complex that enhances the transcriptional activity of Beclin 1. This interaction between AMBRA1 and Beclin 1 is critical for the regulation of autophagy.

The Role of AMBRA1 in Beclin 1 Regulation

AMBRA1 has also been shown to regulate the activity of Beclin 1 in various ways. For example, one study reported that AMBRA1 can inhibit

Protein Name: Autophagy And Beclin 1 Regulator 1

Functions: Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy (PubMed:20921139, PubMed:23524951, PubMed:24587252, PubMed:33854232, PubMed:33854235, PubMed:33854239, PubMed:32333458). The DCX(AMBRA1) complex specifically mediates the polyubiquitination of target proteins such as BECN1, CCND1, CCND2, CCND3, ELOC and ULK1 (PubMed:23524951, PubMed:33854232, PubMed:33854235, PubMed:33854239). Acts as an upstream master regulator of the transition from G1 to S cell phase: AMBRA1 specifically recognizes and binds phosphorylated cyclin-D (CCND1, CCND2 and CCND3), leading to cyclin-D ubiquitination by the DCX(AMBRA1) complex and subsequent degradation (PubMed:33854232, PubMed:33854235, PubMed:33854239). By controlling the transition from G1 to S phase and cyclin-D degradation, AMBRA1 acts as a tumor suppressor that promotes genomic integrity during DNA replication and counteracts developmental abnormalities and tumor growth (PubMed:33854232, PubMed:33854235, PubMed:33854239). AMBRA1 also regulates the cell cycle by promoting MYC dephosphorylation and degradation independently of the DCX(AMBRA1) complex: acts via interaction with the catalytic subunit of protein phosphatase 2A (PPP2CA), which enhances interaction between PPP2CA and MYC, leading to MYC dephosphorylation and degradation (PubMed:25803737, PubMed:25438055). Acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (PubMed:25499913, PubMed:30166453). Acts as a key regulator of autophagy by modulating the BECN1-PIK3C3 complex: controls protein turnover during neuronal development, and regulates normal cell survival and proliferation (PubMed:21358617). In normal conditions, AMBRA1 is tethered to the cytoskeleton via interaction with dyneins DYNLL1 and DYNLL2 (PubMed:20921139). Upon autophagy induction, AMBRA1 is released from the cytoskeletal docking site to induce autophagosome nucleation by mediating ubiquitination of proteins involved in autophagy (PubMed:20921139). The DCX(AMBRA1) complex mediates 'Lys-63'-linked ubiquitination of BECN1, increasing the association between BECN1 and PIK3C3 to promote PIK3C3 activity (By similarity). In collaboration with TRAF6, AMBRA1 mediates 'Lys-63'-linked ubiquitination of ULK1 following autophagy induction, promoting ULK1 stability and kinase activity (PubMed:23524951). Also activates ULK1 via interaction with TRIM32: TRIM32 stimulates ULK1 through unanchored 'Lys-63'-linked polyubiquitin chains (PubMed:31123703). Also acts as an activator of mitophagy via interaction with PRKN and LC3 proteins (MAP1LC3A, MAP1LC3B or MAP1LC3C); possibly by bringing damaged mitochondria onto autophagosomes (PubMed:21753002, PubMed:25215947). Also activates mitophagy by acting as a cofactor for HUWE1; acts by promoting HUWE1-mediated ubiquitination of MFN2 (PubMed:30217973). AMBRA1 is also involved in regulatory T-cells (Treg) differentiation by promoting FOXO3 dephosphorylation independently of the DCX(AMBRA1) complex: acts via interaction with PPP2CA, which enhances interaction between PPP2CA and FOXO3, leading to FOXO3 dephosphorylation and stabilization (PubMed:30513302). May act as a regulator of intracellular trafficking, regulating the localization of active PTK2/FAK and SRC (By similarity). Also involved in transcription regulation by acting as a scaffold for protein complexes at chromatin (By similarity)

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