Antibody News

There are 3 major autophagy pathways- microautophagy, chaperone-mediated autophagy, and macroautophagy. Macroautophagy is the pathway herein referred to as simply autophagy.
Autophagy can be broken down into 4 main stages: phagophore nucleation, autophagosome elongation, autophagosome docking and fusion with a lysosome, and vesicle breakdown and degradation. ATG4A is one of four human ATG4 homologs (ATG4A, ATG4B, ATG4C, and ATG4D) involved in autophagosome elongation. ATG4A encodes a 45 kDa protein called autophagin-2 that is a member of the C54 family of cysteine proteases. Like ATG4B, ATG4A does not require any cleavage to enable its catalytic activity. ATG4A cleaves the ubiquitin-like protein ATG8 to expose a C-terminal glycine, allowing further post-...

FAS-associated death domain protein (FADD) is a 23 kDa adaptor protein involved in initiating apoptosis. FADD is best known for its involvement in extrinsic/death receptor-mediated apoptosis, but it is also involved in initiating necroptosis with serine/threonine kinases RIPK1 and RIPK3 (1). FADD binds to receptors of the tumor necrosis factor (TNF) superfamily through its C-terminal death domain (DD). During extrinsic apoptosis, binding of the Fas-ligand causes trimerization of the Fas-receptor which then binds to FADD via the DD domain. Activated FADD recruits apoptotic pro-caspases to form the death-inducing signal complex (DISC). Formation of the DISC allows cleavage and activation of initiator caspases-8 and -10. Presence of the DD domain is critical to the formation of the DISC and initiation of apoptosis. c-FLIP, PKC, and MKRN1 have all been identified as negative regulators of FADD activity, thus inhibiting apoptosis.

Dysregulation of apoptosis has been...

SLC34A1 encodes the 69 kDa sodium-dependent phosphate transport protein 2A (Npt2a). SLC34A is a member of the type II sodium-phosphate co-transporter family, along with SLC34A3 which encodes Npt2c. These proteins are abundantly expressed along the proximal tubules of the kidneys where most of the filtered inorganic phosphate (Pi) is reabsorbed into the body. Renal reabsorption of Pi directly regulates blood phosphate levels, important for many metabolic processes. While SLC34A1 expression is largely confined to the kidney, it has been identified in tissues from lungs, testes, fallopian tubes, skeletal muscle, and cardiac myocytes. Its role in each of these tissues is yet to be fully characterized.

SLC34A1 mutations have been linked to hypophosphatemia which is characterized by bone demineralization and osteoporosis due to low levels of phosphate in the blood (1). Renal phosphate loss may also lead to the formation of calcium stones /nephrolithiasis (2). Due to...

Monocyte chemotractant protein-1 (MCP-1), also known as CCL2, is a key chemokine involved in the migration of monocytes and macrophages to sites of active inflammation. It is a member of the C-C/beta family of cytokines, characterized by the Cys-Cys sequence at its N-terminus (1). MCP-1 is tethered to endothelial cells via glycosaminoglycans within the plasma membrane (2). MCP-1 cleavage by MMP-12 is necessary for MCP-1 to interact with its receptor CCR2. MCP-1 activation recruits monocytes to vascular endothelium during active inflammation and also for regular immune surveillance. MCP-1 has been implicated to play a role in disorders such as psoriasis, atherosclerosis, multiple sclerosis, and rheumatoid arthritis- all of which display a predominately monocytic infiltrate (3).

Gilbert et. al. used the MCP-1 antibody (5D3-F7) to assess the expression of MCP-1 in testicular...

While known for their role in programmed cell death, caspases are also essential for mediating inflammatory responses and innate immunity. Binding of microbial molecules by pattern recognition receptors triggers the formation of the multiprotein inflammasome complex and the activation of caspase-1 (1). Caspase-1 is then able to mediate the activation and secretion of proinflammatory cytokines including interleukin-1. In addition to caspase-1, caspase-11 also plays an important role during the inflammatory response. Depending on the type of pathogen infection, casapse-11 is needed for caspase-1 activation and the processing of proinflammatory cytokines (1). This alternative pathway to inflammasome activation represents a noncanonical proinflammatory mechanism that is currently under investigation (1). Unlike other caspase family members, expression of caspase-11 is induced by inflammatory stimulation....

Caspases are endoproteases that play important roles in the regulation of cell death and apoptosis. Caspase active sites contain a catalytic cysteine residue essential for the proteolytic cleavage of their substrates at conserved aspartic acid residues (1). Caspases are produced as inactive procaspase monomers in order to regulate their activity. Upon dimerization procaspases are cleaved to produce their active form (1). Caspases are typically grouped by their role in either cell death or inflammation. Inflammatory caspases (caspase-1, -4, -5, -12) are important mediators of the innate immune response. Inflammatory procaspases are activated by the inflammasome, a multiprotein complex formed in response to stimulation of pattern-recognition receptors by pathogen derived molecules such as LPS (1). Activated caspases are then able to facilitate the activation and secretion of inflammatory cytokines (1). Although the precise function of caspase-5 is unclear, its expression...

The 78 kDa glucose-regulated protein (GRP78) is the eukaryotic orthologue to the prokaryotic heat shock 70 kDa protein 5 (HSPA5). GRP78 is also sometimes referred to as BiP. GRP78 is a member of the HSP70 family and plays dynamic roles in protein regulation within the endoplasmic reticulum. GRP78 is the most abundant chaperone in the ER and plays an important role in regulating the unfolded protein response (UPR) (1). GRP78 forms a multiprotein chaperone complex with DNAJB11, HSP90B1, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1, and ERP29. It assists with protein translocation, folding, assembly, and initiation of the UPR. In an unstressed cell, GRP78 also forms a stable complex with IREI, ATF6, and PERK to keep these ER stress sensors in an inactive state. Misfolded proteins relieve the interaction of GRP78 with these proteins, freeing them to initiate the UPR. GRP78 was previously thought to be localized only to the endoplasmic reticulum; however, more recent...

Caspase-2 is a highly conserved member of the caspase family involved in the initiation and execution of apoptosis. While its function is still poorly understood, caspase-2 is thought to be important for apoptosis in response to DNA damage, bacterial infection, or abnormal mitosis (1). Caspase-2 contains an N-terminal caspase recruitment domain, the large p19 subunit containing the active site, and the small C-terminal p12 subunit (1). In response to various apoptotic signals caspase-2 undergoes dimerization. Caspase-2 then promotes its own cleavage into the mature active form consisting of a p19/p12 heterodimer (1).This active/cleaved form of caspase-2 can then cleave and activate pro-apoptotic signaling proteins such as the BCL-2 family protein BID (2). This promotes the release of cytochrome c and the induction of apoptosis (2). BID cleavage by caspase-2 was demonstrated by researchers at the University of California San Francisco (3). They...

CD63 is a type II membrane protein belonging to tetraspanin superfamily and it play key roles in the activation of several cellular signaling cascades along with acting as TIMP1 receptor. It is expressed by activated platelets, monocytes, macrophages, granulocytes, T /B cells, and different type of cancer cells. CD63 localizes to endosomes, lysosomes and on the cellular surfaces, and is often considered as a marker for late endosomes as well as for lysosomes. Besides its major role in regulation of intracellular transport and localization of several proteins, CD63 controls several processes such as cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration (1). Moreover, CD63 plays an essential role during HIV-1 replication and it has been shown to incorporate into HIV-1 virions, and to colocalize with HIV-1 Env and Gag proteins in HIV-1 producing cells (2). Most of the recent studies on CD63...

Ataxia telangiectasia mutated (ATM) is essential for the maintenance of genomic stability. ATM is a 370 kDa serine-threonine kinase that is constitutively expressed in various tissues. Although primarily nuclear, ATM is also found at lower levels associated with cytoplasmic vesicles. As a PI 3-kinase family member, ATM is able to phosphorylate a wide variety of substrates including proteins involved in sensing and repairing DNA damage such as p53 and Brca1 (2). Normally ATM is found as an inactive homodimer. Following ionizing radiation ATM undergoes autophosphorylation and dissociates into catalytically active monomers. Phospho-specific ATM antibodies have aided in the identification of autophosphorylation sites and their roles in the DNA damage response (3). Examination of ATM localization by immunofluorescence using a general ATM antibody has...

Eukaryotic initiation factor 2 (eIF2) regulates global protein translation by binding to Met-tRNA and the 40S ribosome to form the pre-initiation complex. eIF2 is a heterotrimer consisting of alpha, beta, and gamma subunits. The 36kDA eIF2α subunit serves a key regulatory role. Phosphorylation of the serine residue at position 51 is able to block the formation of the pre-initiation complex and halt global protein translation. This regulatory mechanism allows cells to respond and adapt to diverse stresses such as nutrient deficiencies, viral infection, or general ER-stress. The four eIF2α kinases sense and respond to distinct types of stresses. Of these PERK (PKR-like ER kinase) phosphorylates eIF2α in response to ER-stress while GCN2 (general control non-derepressible-2) is activated in response to starvation or nutrient deficiency (1). PKR (protein kinase double-stranded RNA-dependent)...

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. These interactions were studied in detail in a recent study by Sun et al. (1). They used UVRAG antibody in immunoprecipitation experiments to examine the effect of Beclin 1 acetylation on UVRAG-Beclin 1 complex assembly and autophagosome maturation (1). In addition to autophagy the Beclin 1-UVRAG interaction was also shown to be essential for endocytosis and neuron viability (2). McKnight et al. used...