Antibody News

Scavenger's Helper - SR-BI (scavenger receptor class B member 1, SCARB1)

Friday, June 20, 2014 - 13:00

SR-B1 belongs to the CD36 scavenger receptor family and serves as a receptor for several ligands including phospholipids, cholesterol ester, lipoproteins, phosphatidylserine, and caveolae localized HDL. It is expressed in endothelial cells, macrophages, and dendritic cells. It facilitates the flux of both free and esterified cholesterol between the cell surface and extracellular donors and acceptors (HDL and to a lesser extent, apoB-containing lipoproteins and modified lipoproteins). Thus SR-B1 plays an important role in meditating the uptake of HDL-derived cholesterol and cholesterol ester in both liver and steroidogenic tissues. It also appears to be involved in the phagocytosis of apoptotic cells, uptake of lipid soluble vitamins (vitamin E and carotenoids), as well as pathogen recognition, and the anti-inflammatory response. SR-BI has also been involved in the capture and cross-presentation of antigens from viruses, bacteria and...

IRAK4: The "master IRAK" critical for initiating immune responses

Thursday, June 19, 2014 - 13:30

IRAK4, also known as Interleukin-1 receptor-associated kinase 4, is a serine/threonine-protein kinase that plays a critical role in initiating innate and adaptive immune responses against foreign pathogens. It activates NF-kappaB in both Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways.

IRAK-4 belongs to a family of mammalian IRAKs that include IRAK-1 [11], IRAK-2 [12], and IRAK-M, also known as IRAK-3 [13]. Out of the four members in the mammalian IRAK family, IRAK-4 is considered to be the “master IRAK”, the only family member indispensable for IL-1R/TLR signaling. In humans, mutations resulting in IRAK-4 deficiency have been linked to susceptibility to bacterial infections, especially recurrent pyogenic bacterial infections. Though characterized functionally as a serine/threonine kinase, the crystal structures revealed that...

ASC-2: An important co-activator of different nuclear receptors

Wednesday, June 18, 2014 - 14:58

ASC-2, also known as Nuclear Receptor Co-Activator 6, directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. It is involved in the co-activation of different nuclear receptors, such as for steroids (GR and ERs), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). It is believed to function as a general co-activator, rather than just a nuclear receptor co-activator. It may also be involved in the co-activation of the NF-kappa-B pathway and co-activate expression via remodeling of chromatin and its interaction with histone acetyltransferase proteins. Diseases associated with ASC-2 include thyroiditis and AIDS dementia complex.  Among its related super-pathways are Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) and Metabolic pathways.

Using Novus NB200-336 ASC-2...

LYVE1 - It's Alive! It's a LYVE

Monday, June 16, 2014 - 10:50

LYVE1 (lymphatic vessel endothelial hyaluronan receptor-1) is one of the most specific and widely used mammalian lymphatic endothelial markers.It is found in lymph nodes and at the luminal/abluminal surfaces of lymphatic vessels. It is a single-pass type I membrane protein that exists in a disulfide-linked homodimer form. LYVE1 undergoes ligand-dependent internalization and recycling at the cell surface, and exhibits ligand-specific transporter trafficking between intracellular organelles and the plasma membrane. It plays a key role in the autocrine regulation of cell growth mediated by growth. LYVE1 also behaves as hyaluronan transporter, either mediating its uptake for catabolism within lymphatic endothelial cells themselves, or its transport into the lumen of afferent lymphatic vessels for subsequent re-uptake and degradation in lymph nodes. A group at ImClone employed the LYVE1 antibody in their...

CD81/TAPA1: I'm on Tapa the Cell

Friday, June 13, 2014 - 10:07

Target of the antiproliferative 1 (TAPA1), also known as CD81, is found in the plasma membrane in lymphocytes and plays an important role in the regulation of lymphoma cell growth. This transmembrane 4 superfamily (TM4SF) protein is primarily found on CD4+CD8+ thymocytes as well as broadly in the periphery, with high-level expressed in cell cohorts such as B-cells, NK cells, macrophages, and dendritic cells. CD81 appears to be involved in a variety of cellular immune processes such as activation, proliferation, and differentiation. It is believed to act as a viral receptor for HCV. Mutations affecting CD81 cause immunodeficiency - characterized by antibody deficiency, recurrent bacterial infections, and hypogammaglobulinemia. The activation of T-cells induces CD81 upregulation. Yoshie’s group at the Shionogi Medical Institute developed the M38 clone of the CD81 antibody in...

IRE1 alpha - stress no more!

Thursday, June 12, 2014 - 16:37

The unfolded protein response (UPR) is a eukaryotic cell mechanism that copes with ER stress and is initiated by three ER-localized sensors: PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 alpha (IRE1 alpha). The UPR-responsive downstream signaling is regulated through the ATF6 and IRE1-XBP1 pathways. UPR serves three important mechanisms: inhibiting protein translation to restore normal cell function; increasing production of protein folding-involved chaperones; and activating misfolded protein ubiquitination for targeting and degradation. When the ER-stress is not appropriately relieved, UPR leads to the fail-safe of apoptosis. IRE1 alpha is a single-pass type I membrane protein within the ER membrane, and is ubiquitously expressed, with high levels particularly in the pancreas. It exhibits autophosphorylation and under ER stress conditions, is ADP-ribosylated by...

CD206 - a potential candidate for targeted delivery of therapeutics

Wednesday, June 11, 2014 - 16:18

Macrophage mannose receptor 1 (MRC1), also known as CD206, is a Pattern Recognition Receptor (PRR). PRRs are expressed by antigen processing and presentation cells, and are activated upon detection of Pathogen-Associated Molecular Patterns (PAMPs). PAMPs are molecular sequences shared by large groups of pathogens, which are essential for microbial survival and/or pathogenicity and include cell wall components such as glycoproteins. Many glycoproteins derived from bacteria and fungi are mannosylated, and CD206 is specifically involved in the recognition of these molecules, resulting in endocytosis of the micro-organisms which express them.

CD206 is a type I transmembrane protein that belongs to the C-type lectin family, and is expressed by macrophages and dendritic cells (1). Macrophages can be...

LOX: A prime enzyme

Tuesday, June 10, 2014 - 08:46

LOX is a copper-dependent amine oxidase enzyme that executes post-translational oxidative deamination on peptidyl lysine residues in precursors of fibrous collagen and elastin. LOX is secreted into the extracellular environment in an inactive form, where it is processed into an active form. Its activity is crucial for maintaining both the tensile and elastic properties of connective tissue residing within skeletal, pulmonary, and cardiovascular systems. Furthermore, its expression is highly regulated during normal development and uncontrolled expression or activity has been documented in a wide range of predominantly ECM diseases.  These diseases include, but are not limited to, myocardial ischemia/heart failure, atherosclerosis, scleroderma, liver cirrhosis, glaucoma, Alzheimer's/non-Alzheimer's dementia, and Wilson's disease. In addition to its matrix modifying functions, LOX is also heavily implicated as a tumor suppressor.

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IKK alpha says "no" to NFk beta

Thursday, June 5, 2014 - 16:19

The nuclear factor kappa B (NFkB) is a ubiquitous transcription factor essential for the activation of immune and inflammatory responses. NFkB activity is inhibited when it is associated with IkB proteins in the cell cytoplasm. IkB proteins are phosphorylated by the IkB kinase complex. The IKK serine protein kinase consists of alpha and beta subunits (IKK alpha and IKK beta). These subunits interact with each other and together, are essential for NFkB activation. IKK alpha is expressed in variety of human tissues. The targeted disruption of the IKK alpha gene in mice results in severe skin and limb abnormalities and newborn death. USCD researchers used an IKK alpha antibody to identify specific protein functions dependent on catalytic activity1. They determined that during mammary gland development, IKK alpha is an essential link connecting RANK and cyclin D1 expression....

A Big Guy for the Catecholamine Synthesis - Tyrosine hydroxylase (TH)

Wednesday, June 4, 2014 - 16:23

In the synthesis pathway for the catecholamines - dopamine, epinephrine, and norepinephrine, tyrosine hydroxylase is the rate-limiting enzyme. Through alternative mRNA splicing, a wide molecular diversity of TH isoforms are generated that are tissue-specific and carry varied enzymatic activities, allowing for differential neurotransmitter availability at various synapses. The devastating condition of Parkinson's disease (PD) is due to a TH deficiency, where dopaminergic neuron degeneration and low dopamine levels consistently are present, along with gross neurochemical abnormalities when monitored by tyrosine hydroxylase antibody staining1. Tyrosine hydroxylase antibody staining patterns in postmortem PD brain samples indicate that phosphorylation at the N-terminus of...

LAMP2: Protector of the lysosome

Monday, June 2, 2014 - 13:25

LAMP2 belongs to the family of membrane glycoproteins who confer selectins with carbohydrate ligands. LAMP2 has been implicated in tumor cell metastasis, as well as overall protection, maintenance, and adhesion of the lysosome. It appears that LAMP2 may protect the lysosomal membrane from autophagy, as well as maintain the required acidic environment necessary for proper function.  LAMP2 is a single-pass type I membrane protein that shuttles between endosomes, lysosomes, and the plasma membrane. Bhandari’s group performed immunofluorescence using a LAMP2 antibody to characterize the E3 ubiquitin atrophin-interacting protein 4 (AIP)-arrestin-2 complex and its regulation of chemokine receptor CXCR4 sorting in endsomes1. LAMP2 mutations result in the lysosomal glycogen storage disease "Danon Disease", which is characterized by the accumulation of autophagic material in striated myocytes. This breakthrough...

CD45 - Much more than just a housekeeping protein

Friday, May 30, 2014 - 13:47

CD45, also known as T200 or the Leukocyte Common Antigen (LCA), is encoded by the Protein Tyrosine Phosphatase Receptor type C (PTPRC) gene. The protein is expressed exclusively on cells of the haematopoietic system, and is one of the most abundant leukocyte cell surface glycoproteins (1). Different isoforms of CD45 are found on specific lymphocyte sub-populations, and are generated by alternative splicing. (2). At least four variants of the human protein can be distinguished by electrophoresis, with molecular weights ranging from 180-220kDa (3). B cells have been shown to express a 220kDa protein, while thymocytes express a 180kDa variant (2).

CD45 is a member of the Protein Tyrosine Phosphatase (PTP) family, which is comprised of more than 100 human genes (4). PTPs were originally believed to be housekeeping proteins, responsible simply for the dephosphorylation of tyrosine residues, however they are now known to play key...

TRPM8: The Multi-functional Ion Channel

Thursday, May 29, 2014 - 16:05

TRPM8 is a transmembrane homo-tetramer ion channel that is activated by cold temperatures, cooling agents, and menthol stimuli. It belongs to a subgroup within the larger family of TRP cation channels (including the TRPV1 capsaicin receptor) that are named after the melastatin protein. These proteins are also known chanzymes due to their C-terminus enzyme domains. TRPM8 contains a voltage sensor as well as a binding domain for channel agonists such as menthol and icilin. Upon activation, it allows sodium and calcium entry, causing the creation of an action potential through depolarization. It is expressed in sensory neurons where it appears to play a role in neurite outgrowth, signaling, and apoptosis in response to noxious stimuli.

Immunohistochemistry: TRPV1 Antibody...

Melanoma Infographic

Tuesday, May 27, 2014 - 12:48

Melanoma is caused by DNA damage to melanin producing cells. Common warning signs of melanoma are changes in color, size, and shape of skin/moles, new growth areas on the skin, and sores that do not heal. Protection from sun exposure and ultraviolet rays as well as regularly examining changes to skin are important for prevention.

Melanoma Infographic

Resources

  1. Cancer.org 
  2. Skincancer.org ...

You can't be without me - SNF5

Friday, May 23, 2014 - 13:19

The protein encoded by SNF5 is a component of the chromatin-remodeling protein complex responsible for relieving repressive chromatin structures by allowing the transcriptional machinery to access targets more effectively. SNF5 has been found to be a tumor suppressor, and mutations within it are associated with some malignant tumors. Two transcript variants encoding different isoforms exist. Scurr’s group published interesting findings on effector proteins in senescence in Cell1. There, they immunoblotted with the SNF5 antibody to monitor B-Raf and IGFBP7 protein expression levels in several melanoma cell lines, and found that lentiviral-silencing of secreted IGFBP7 does not affect  senescence in melanocytes and fibroblasts.

p73: An Important Tumor Suppressor Cousin of p53

Thursday, May 22, 2014 - 16:06

p73 has been identified as a long-lost cousin of the p53 tumor suppressor protein. It has high homology with both p53 and with p63, a gene implicated in the maintenance of epithelial stem cells. The presence of significant homology between the DNA-binding domains of p53, p63, and p73 suggest that they have overlapping functions. Targeted disruption of p73 leads to defects hippocampal dysgenesis, hydrocephalus, chronic inflammation, and infections. A German group used the p73 antibody in immunoprecipitation studies using directed expression of dominant-negative p73 to restore cell cycle progression in cardiomyocytes and improve cardiac regeneration1. Kravchenko’s group examined the ability of the small molecule RETRA to suppress mutant-bearing cancer cells using the p73 antibody2. Based on their studies, it appears that a mutant p53-73...

OS9: Taking proteins to the ER finish line

Wednesday, May 21, 2014 - 15:01

The OS9 protein is a lectin/glycoprotein that maintains endoplasmic reticulum (ER) quality control and ER-associated degradation (the so-called ERAD pathway) of newly synthesized proteins. It is essential for the recognition of terminally misfolded non-glycosylated proteins and improperly folded glycoproteins, and binds to them to allow first their retention in the ER, and then second, subsequent transfer to the degradation machinery. The cation-selective channel TRPV4 is OS9's major target. OS9 forms part of the HRD1 ubiquitin ligase complex (SYVN1/HRD1 and SEL1L) which is involved in the retro-translocation of misfolded proteins from the ER to cytosol for ubiquitin-dependent degradation. OS9 has been shown to specifically protect some proteins from this process before maturation, ensuring biological functionality.

Caspase 6, responsible for apoptosis execution

Monday, May 19, 2014 - 14:35

Caspase 6, also known as Apoptotic protease Mch-2, belongs to the peptidase C14A family. It functions as a downstream enzyme in the caspase activation cascade and is responsible for the execution of apoptosis. Its overexpression promotes programmed cell death.

Diseases associated with CASP6 include thoracic cancer and myocardial infarction.  Among its related super-pathways are DR3 Signaling and Apoptosis and the survival FAS signaling cascade.

A clinically relevant model of transient global brain ischemia involving cardiac arrest followed by resuscitation in dogs was utilized to study the expression and proteolytic processing of apoptosis-regulatory proteins. Immunohistochemical analysis using antibodies, which recognize processed caspase-3, -6, -8, and -10, provided evidence of time-dependent activation of these proteases in both neurons and glia in ischemia-sensitive regions of the brain....

MMP2: The extracellular matrix bids you adieu

Friday, May 16, 2014 - 08:35

MMP2 is a peptidase enzyme that belongs to the large family of matrix metalloproteinases (MMPs) which degrade the extracellular matrix (ECM) with different substrate specificities. Aberrant and unregulated expression of MMPs via deregulation of key negative check controls is strongly associated with increased tumor invasiveness, metastasis potential, and angiogenesis. This uncontrolled behavior is in direct contrast to the tightly controlled physiological systems of embryonic development, tissue remodeling, and rebuilding. MMP2 antibody immunostaining was paired with sophisticated computed tomography as viable prognostic indication assessment method for small lung adenocarcinomas1.  The Japanese group that did these studies also identified CD34, MMP9, VEGF, and TIMP-2 as other markers. Ribeiro-Silva’s...

Survivin is thrivin'

Wednesday, May 14, 2014 - 14:27

The survivin anti-apoptotic protein is the smallest member of a large family of proteins such as X-linked IAP, c-IAP1 and 2, IAP-like protein-2, melanoma IAP, Livin, and NAIP. Survivin regulates basic physiological events such as the cell cycle, tumor progression, fetal development, and cell migration. To further characterize and better understand apoptotic pathways, Xu’s group at MD Anderson used a survivin antibody in a DNA microarray screen upon promyelocytic leukemia protein (PML) target genes1. With their data, they identified a new PML4-dependent pathway that culminated in survivin as its main downstream target.

TLR9: For Whom the Cell Tolls

Monday, May 12, 2014 - 15:03

The Toll-like receptor 9 (TLR9) protein, also known as CD289, belongs to the family of Toll-like receptor (TLR) proteins which play a large role in pathogen recognition and the activation of innate immunity. Scientists using TLR9 antibodies have found that TLRs are highly conserved from Drosophila to humans, with a high degree of structural and functional homology1,2. TLR proteins in general recognize pathogen-associated molecular patterns (PAMPs) present on a diverse range of exogenous and endogenous ligands – including infectious agents - and regulate the cytokine production required for effective immunity development. Specifically, TLR9 detects unmethylated CpG dinucleotides. Studies in human glioblastoma with the TLR9 antibody found varying TLR9 RNA levels, suggesting that treatment with immunostimulating...

Gli is a top nominee in cancer research

Thursday, May 8, 2014 - 15:49

Glioma-associated oncogene 1 (Gli1) is a transcription factor within the DNA-binding zinc-finger protein family. The Sonic Hedgehog signaling pathway (SHH), which assists in embryonic development and maintaining stem cell populations in adults, activates the Gli1 protein. In the SHH Pathway, the hedgehog ligand binds to patched transmembrane protein receptor (PTC). PTC is an inhibitor of SMO, a protein receptor, and when the hedgehog ligand is present, SMO is not inhibited. Gli1 can then activate transcription along with a few other proteins, including Gli2 and Gli3. It is here that abnormal signaling from the SHH can lead to dysfunctional cells and cancer.

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53BP1 - DNA damage is no fun

Wednesday, May 7, 2014 - 09:20

The 53BP1 (p53 binding protein 1) was initially believed to be a p53 transcriptional enhancing partner, but it has now been established as an ataxia telangiectasia mutated (ATM) substrate. As a late DNA damage response (DDR) marker, 53BP1 appears during the telophase and cytokinesis phase of mitotic mammalian cells1. This was discovered when a 53BP1 antibody was applied to mitotic cells to demonstrate the absence of a full DDR response that was also sensitive to suppression by high levels of cyclin-dependent kinase1 (CDK1) activation. Additionally, the ubiquitination cascade was known to be involved in 53BP1 recruitment to DNA damage sites within cells, but Mallette’s group used a 53BP1 antibody to pinpoint the degradation of the JMJD2A/KDM4A tandem tumor domain via an E3 ubiquitin ligase ...

GAPDH (Glyceraldehyde 3-Phosphate Dehydrogenase)

Thursday, May 1, 2014 - 16:05

GAPDH is a 146 kD tetramer glycolytic pathway metabolic enzyme responsible for reversibly phosphorylating glyceraldehyde 3-phosphate. It may have other possible functions in transcriptional activation. GAPDH is highly expressed due to this housekeeping role, and its prevalent expression has allowed its use as an internal loading control – traditionally for mRNA expression comparisons – but also in protein studies. The GAPDH antibody is an excellent standard as reflected in its universal use as such in a wide range of scientific experiments and published literature.  The GAPDH antibody was employed to analyze the effect of the tumoricidal protein-lipid complex HAMLET upon cancer cells, where it was found that that HAMLET not only killed cancer cells but also activated an innate immune response in the surrounding tissues via ion channel activation and homeostasis disruption1.

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NFkB3-p65: Say that three times fast!

Wednesday, April 30, 2014 - 15:19

NF-kappa-B is a ubiquitous transcription factor involved in several biological processes such as inflammation, immunity, differentiation, cell growth, tumor genesis and apoptosis. Unlike the majority of transcription factors that reside in the nucleus, NFkB is predominantly bound to IkBs protein inhibitors and is located in the cytoplasm. There are two major signaling pathways involved in the activation of NFkB, canonical and non-canonical. [1] In the canonical NF-kB pathway, NF-kB activation is dependent on the inducible degradation of IkBs, particularly IkBa.  This leads to nuclear translocation of various NF-kB complexes, predominantly the p50/RelA dimer.  The non-canonical pathway activates the RelB/p52 NF-kB complex using a mechanism that relies on the inducible processing of p100 instead of degradation of IκBα. [1,2]

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