AMBRA1


Description

The AMBRA1 (autophagy and beclin 1 regulator 1) is a protein-coding gene located on chromosome 11.

AMBRA1 (activating molecule in Beclin1-regulated autophagy) is a protein that can regulate cancer cells through autophagy. AMBRA1 is described as a mechanism cells use to divide, and there is new evidence demonstrating the role and impact of AMBRA1 as a candidate for the treatment of several disorders and diseases, including anticancer therapy. It is known to suppress tumors and plays a role in mitophagy and apoptosis. AMBRA1 can be found in the cytoskeleton and mitochondria, and during the process of autophagy, it is localized at the endoplasmic reticulum. In normal conditions, AMBRA1 is dormant and will bind to BCL2 in the outer membrane. This relocation enables autophagosome nucleation. AMBRA1 protein is involved in several cellular processes and is involved in the regulation of the immune system and nervous system.

== Function == AMBRA1 serves to regulate the process of autophagy, which is the cellular breakdown and recycling of unnecessary or damaged cellular components. This protein interacts with other proteins and genes to initiate the formation of autophagosomes, an essential component of autophagy. Cellular processes such as cell proliferation, apoptosis, and cellular metabolism are regulated through the interactions between AMBRA1 and other proteins.

AMBRA1 is a protein that acts as a substrate-recognition component in a protein complex called DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase. This complex is involved in regulating the cell cycle and autophagy. AMBRA1 specifically targets and binds to phosphorylated cyclin-D proteins (CCND1, CCND2, and CCND3), leading to their ubiquitination and subsequent degradation by the DCX complex. This process is essential for the transition from the G1 to S phase of the cell cycle. AMBRA1 also plays a crucial role in autophagy, the process by which cells break down and recycle damaged or unnecessary components. It interacts with proteins like BECN1, PIK3C3, ULK1, and TRAF6, mediating ubiquitination events that activate autophagy. Furthermore, AMBRA1 promotes the degradation of MYC, a key regulator of cell growth, by interacting with protein phosphatase 2A (PPP2CA). It also regulates the CRL5 ubiquitin ligase complex through ubiquitination of Elongin-C. AMBRA1's ability to control these processes contributes to its tumor suppressor function, ensuring genomic integrity and preventing abnormal cell growth. It interacts with various proteins, including BECN1, BCL2, ULK1, PPP2CA, DYNLL1, DYNLL2, TRAF6, TRIM32, PRKN, LC3, HUWE1, and others, to regulate cell cycle progression, autophagy, mitophagy, and Treg cell differentiation.

AMBRA1 is also known as DCAF3, WDR94.

Associated Diseases



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