Beclin 1

TRIF, also known as toll like receptor adaptor molecule 1 or TICAM1, is known for its role in invading foreign pathogens as part of our innate immune response. TRIF/TICAM1 is a TIR-domain adaptor protein (toll/interleukin-1 receptor) that interacts with the Toll-like receptors (TLRs) through intracellular signaling and recognition of its TIR site.

UV resistance-associated gene (UVRAG) is a tumor suppressor that is commonly mutated in colon and breast cancer. While UVRAG was discovered for its ability to complement UV sensitivity in xeroderma pigmentosum cells, its main functions are in autophagy, endocytosis, and apoptosis. During autophagy UVRAG interacts with Beclin 1 to promote autophagosome formation. UVRAG can also interact with VPS16 to recruit membrane fusion machinery to mediate autophagosome maturation.

C/EBP homologous protein (CHOP) is a transcription factor that regulates apoptosis in response to cellular stress. CHOP also known as growth arrest and DNA damage 153 (GADD153) was first cloned because of its induction in response to genotoxic stress such as UV irradiation. CHOP has now been shown to be induced mainly by ER-stress (1). CHOP is normally expressed at low levels and localizes to the cytoplasm. Cellular stress triggers an upregulation of CHOP levels and accumulation in the nucleus where it can act as either a transcriptional repressor or activator (1).

The Beclin 1 protein is a central regulator of autophagy in mammalian cells. Autophagy is an essential process used to maintain cellular homeostasis by degrading and recycling cellular components such as damaged or worn out organelles and macromolecules. Autophagy is also activated in response to cellular stresses such as nutrient starvation or intracellular pathogens and can protect the cell from programmed cell death.

ATG9A is the only essential integral membrane protein involved in autophagy. ATG9A contains six transmembrane domains and initiates the assembly of autophagosomes. The autophagosome is a double-membrane structure that engulfs and eventually degrades cytoplasmic materials such as organelles or macromolecules. Assembly of the autophagosome requires the delivery of lipids and membrane components to initiate and expand the double-membrane pre-autophagosome structure called the isolation membrane.

Beclin 1 is the first mammalian gene identified as a mediator of autophagy, and plays important roles in development, tumorigenesis, and neurodegeneration.

Beclin 1 is the mammalian orthologue of the yeast Apg6/Vps30 gene. Beclin 1 can complement the defect in autophagy present in apg6 yeast strains and stimulate autophagy when overexpressed in mammalian cells (1) and can bind to Bcl2, an important regulator of apoptosis (2) suggesting a role in two fundamentally important cellular pathways: autophagy and apoptosis.