Antibody News

Succinate dehydrogenase is an important tetrameric protein involved in the citric acid cycle. It is localized to the inner mitochondrial membrane of cells. Succinate dehydrogenase makes up Complex II of the electron transport chain (ETC) and is responsible for the conversion of succinate to fumarate. This enzymatic reaction also generates a molecule of FADH2, harnessed by the ETC to make energy for the cell. SDHA, the flavoprotein subunit of the succinate dehydrogenase tetrameric complex, interacts with SDHB, SDHC, and SDHD in the complex. SDHA oxidizes succinate by deprotonating the α-carbon and transferring the proton to the FAD cofactor to generate FADH2. SDHA has been identified as a tumor suppressor gene (1). SDHA mutations have been implicated in the pathogenesis of a neuroendocrine tumor known as a paraganglioma. Other mutations in the SDHA gene can cause dysfunction of the entire succinate dehydrogenase complex, resulting in a condition known as mitochondrial...

Actin is the widely studied and ubiquitous cytoskeletal protein capable of forming dynamic microfilament structures. These filaments are essential for diverse cellular functions including cell shape, migration, cytokinesis, and intracellular trafficking (1). Actin is present in three main isoforms: alpha, beta, and gamma. These globular actin isoforms (G-actin) assemble into dynamic filamentous polymers called F-actin. This process is highly regulated by various actin-binding proteins that affect the stability, organization, and depolymerization of F-actin (1). Given its constitutive high expression, actin is considered a housekeeping gene and easily serves as an internal reference in protein and gene expression studies. Actin transcripts are easily detected through qPCR while western blotting with actin antibodies can provide a convenient loading control. While typically high in expression, beta-actin (ACTB) is further...

Parkin/PARK2 is a cytosolic enzyme which gets recruited to cellular mitochondria damaged through depolarization, ROS or unfolded proteins accumulation, and exert protective effects by inducing mitophagy (mitochondrial autophagy). Parkin induces mitophagy by promoting mitofission (mitochondrial division) and by ubiquitinating mitochondrial proteins to facilitate their recognition/recruitment to the autophagosomal surface. It is a RING-in-between-RING (RBR) E3 ligase which is capable of mediating mono, multi-mono and polyubiquitylation of several proteins including MFN1, MFN2, Miro, BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746, AIMP2 etc. Mutations in PARK2 gene are the most common cause of autosomal recessive Parkinson’s disease (1). Studies implicating PINK1−/− and Parkin−/− mutant Drosophila flies have shown similar mitochondrial abnormalities, as well as neuronal loss and motor deficits, and that Parkin can...

The Role of Caspase-3 in Apoptosis

Caspase-3 enzyme is a member of the family of endoproteases which regulate inflammation and apoptosis signaling networks. Caspase-3 is known as an executioner caspase in apoptosis because of its role in coordinating the destruction of cellular structures such as DNA fragmentation or degradation of cytoskeletal proteins (1). The activity of caspase-3 is tightly regulated and it is produced as zymogen in an inactive pro-form (1). Caspase-3 antibodies serve as excellent biomarkers to monitor induction of apoptosis by detecting the levels of pro caspase-3 and its active form. Cleavage and activation of pro caspase-3 is catalyzed by caspase-8, caspase-...

Caspase-7 is an effector caspase with important roles in mediating cell death signaling. As an effector caspase, caspase-7 is cleaved and activated by initiator caspases such as caspase-1 (1). Like other caspase family proteins, caspase-7 contains a catalytic cysteine residue in its active site. This allows caspase-7 to cleave various substrates, such as PARP, to aid in the degradation and destruction of the cell (2). Mutations in caspase-7 have been found in numerous cancers demonstrating the importance of caspase-7 mediated apoptosis in preventing tumorigenesis (1). Caspase-7 shows some functional redundancy with caspase-3 as both they share a number of the same substrates. However both of these effector caspases have distinct functions during apoptosis. Recent studies have indicated caspase-3 is needed for efficient cell killing and can also block ROS production (3). Caspase-7, on the...

Succinate dehydrogenase (SDH) is a highly conserved protein complex located on the inner mitochondrial membrane where it functions during the Krebs cycle by oxidizing succinate to fumarate (1). This reaction is also important for feeding electrons into the electron transport chain. SDH complex contains four subunits: SDH-A, -B, -C, and -D. Mutation of SDH-A often leads to mitochondrial encephalopathy while mutations to subunits B, C, and D lead to tumors of the head and neck (1).

Belinsky et al. performed immunohistochemistry using SDHA antibody to identify SDH complex deficiency in patient samples and found that bi-allelic inactivation of SDHA is common in gastrointestinal stromal tumors (2). Following staining with the SDHA antibody, samples were sequenced and verified to contain various inactivating mutations. This SDHA antibody based method of...

Caspases are typically known for their role in cell death. However some caspases have recently been investigated for their function during cell proliferation and differentiation. Of these caspase-14 shows a unique expression pattern in the skin and appears to be involved in keratinocyte differentiation. Procaspase-14 is detected in the stratifying epithelium while activated caspase-14 is found only in terminally differentiated keratinocytes (1). Caspase-14 activity is not involved in apoptosis. Instead, caspase-14 is important for keratinization of the epithelium. One of the substrates of activated caspase-14 is profilaggrin, a structural protein that interacts with keratin (1). During keratinization profilaggrin is cleaved into filaggrin monomers to help form a tightly packed and extensively cross-linked keratin matrix (1). Blocking filaggrin processing by caspase-14 results in defects in water retention and protection from UVB irradiation...

Transforming growth factor-beta receptor III (TGF-beta RIII) is one of three receptors for the secreted growth factor TGF-beta. Unlike type I and type II TGF-beta receptors, TGF-beta RIII does not participate directly in the propagation of intracellular signaling in response to TGF-beta binding (1). TGF-beta RIII typically functions as a coreceptor for TGF-beta by binding the ligand with high affinity in order to regulate signaling. TGF-beta RIII contains a large glycosylated extracellular domain and a small intracellular domain. The extracellular domain can bind ligand and enhance TGF-beta signaling. The receptor can also inhibit signaling by binding to and sequestering ligand (1). One study measured the effect of secreted TGF-beta RIII on sequestration of TGF-beta (2). They performed ELISA with TGF-beta RIII antibody to measure the amount of the secreted protein. Their data demonstrated the...

Cathepsins are a family of lysosomal proteases (serine, aspartic and cysteine proteases) that acts in conjunction with lipases and nucleases to degrade biological macromolecules in the lysosomes (1). While most cathepsins are ubiquitously expressed to support normal lysosomal degradation, cathepsin B is unique for its role in various pathologies and malignancies (2). Cathepsin B is often overexpressed and alternatively spliced in cancer cells (2). Increased levels of cathepsin B lead to its secretion where it contributes to metastasis through the degradation of extracellular matrix proteins. Cathepsin B also has neuroprotective effects in neurological disorders such as Alzheimer’s and Huntington’s diseases. In these disorders, cathepsin B contributes to the degradation of toxic protein aggregates through autophagy (2).

The role of cathepsin B in diverse cellular processes makes it an important target and ...

Aside from their important role in apoptosis, caspases also play an important role in inflammatory processes. Humans express four inflammatory caspases: Caspase-1, -4, -5, and -12. Caspase-12 is a 48 kDa protein localized to the ER and involved in the ER stress response. Caspase-12 contains a caspase-associated recruitment domain (CARD) and two catalytic domains, p20 and p10 (1). The ER stress response is important for maintaining ER homeostasis to allow proper lipid synthesis, calcium storage, and protein folding and maturation. The ER stress response is also known as the unfolded protein response (UPR) and ultimately results in apoptosis. The UPR can be triggered by two mechanisms- a transcription factor-dependent pathway or a caspase-dependent pathway. Caspase-12 plays an important role in...

Antibodies play an important role in the innate immune system by circulating in the bloodstream to fight off invading pathogens. IgG is the most prevalent of the five classes of antibodies (IgA, IgD, IgE, IgG, and IgM) and is the only one transmitted from a mother to her offspring. IgG is transported across the epithelium of the placenta by the neonatal Fc receptor (FcRn) (1). FcRn is a 40 kDa protein encoded by the FCGRT gene. FcRn binds to the Fc domain of IgG and transports the antibody in a pH dependent mechanism. Outside of the neonatal period, FcRn continues to play a role in IgG regulation. FcRn binds to IgG in the serum to prolong the half-life of this immunoprotective antibody. It has also been suggested that FcRn binds to albumin and serves the same protective purpose (2). Modification of the FcRn-IgG interaction is being studied as a strategy to increase the lifespan of therapeutic antibodies or to shorten the lifespan of pathogenic antibodies, such as those...

alpha-Synuclein is a 14 kDa protein encoded by the SNCA gene that is abundantly expressed in neurons. Within the neuron, alpha-Synuclein is densely localized on presynaptic terminals, indicating a potential role in synaptic transmission. Nitration at specific tyrosine residues promotes misfolding and aggregation of alpha-Synuclein. These aggregates are a major component of Lewy bodies, characteristic lesions of neurodegenerative disorders known as synucleinopathies. Synucleinopathies include Parkinson’s disease, Alzheimer’s disease, dementia with Lewy bodies, and others. Mutations in the SNCA gene have been linked to autosomal dominant hereditary Parkinson’s disease (1). Recent studies suggest that alpha-Synuclein may interfere with neuroprotective pathways such as insulin signaling (2).It is still unclear exactly how alpha-Synuclein aggregates contribute to the neuronal damage associated with these conditions.

Giasson et...