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Antibody News

CD19: An Undoubted Biomarker for B Cells

Wednesday, September 17, 2014 - 15:16

CD19 is a cell surface protein member of the large immunoglobulin superfamily that complexes with CD21, CD81, and CD225 in the membrane of mature B-cells. A major function of CD19 is to assemble with the antigen receptor of B-lymphocytes to decrease the threshold for receptor-dependent stimulation, thus enhancing the specificity and sensitivity of B-cells towards antigens. CD19 plays a large role in regulating B-cell growth. Its expression is confined to only B-lymphocytes and follicular dendritic cells of the hematopoietic system. Leukemia phenotype studies suggest that CD19 is the earliest and broadest B-cell restricted marker. Because increased CD19 expression stimulates autoantibody production, CD19 studies provide insight into the autoimmunity process.

Glucose-6-phosphatase (G6PC) - A key to regulate your blood sugar level!

Tuesday, September 16, 2014 - 15:17

The integral endoplasmic reticulum membrane-based enzyme G6PC hydrolyzes its substrate glucose-6-phosphate into glucose. Specifically, G6PC breaks down D-glucose 6-phosphate to D-glucose and orthophosphate. Because G6PC forms with the glucose-6-phosphate transporter (SLC37A4/G6PT), the resulting complex is responsible for glucose production. Thus, G6PC is the key enzyme in glucose homeostasis, functioning in both the processes of gluconeogenesis and glycogenolysis. Defects in the enzyme cause glycogen storage disease type I (von Gierke disease). Not surprisingly, G6PC is localized mainly in the liver and kidneys.  It is unique in that it is membrane-bound, unlike most other enzymes that act upon water soluble substrates.

CD14 - TLR4 is my friend in battle against infections!

Monday, September 15, 2014 - 15:37

CD14 is a well-characterized cell-activating receptor for lipopolysaccharide-binding protein (LBP) and peptidoglycan. It is an important modulator for lipopolysaccharide (LPS)-dependent signaling and is a component of the multi-protein complex containing also containing MD2 and toll-like receptor 4 (TLR4). CD14 is an important component of the innate immune response preferentially expressed on mature cells of monocyte lineage. The CD14 protein contains eleven leucine-rich repeats (LRRs). It is also known to be involved in the apoptotic cell clearance, cell surface adhesion molecule upregulation, and IgE level regulation.  It exists in two forms:  a glycosylphosphatidylinositol-anchored membrane protein (mCD14) and a monocyte or liver-derived soluble serum protein (sCD14) which lacks the anchor. sCD14 plays a role in LPS sensitivity to cells lacking the membrane form, and its increased expression is thought to be associated with...

Von Willebrand Factor: An important mediator and carrier of hemostasis

Thursday, September 11, 2014 - 15:44

Human Von Willebrand Factor (factor VIII R: Ag) is a 270 kDa multimeric plasma gylcoprotein. Important in the maintenance of hemostasis, it mediates platelet adhesion to injured vessel walls and serves as a carrier and stabilizer for coagulation factor VIII. The Von Willebrand factor has functional binding domains to platelet glycoprotein Ib, glycoprotein IIb/IIIa, collagen and heparin. The factor is synthesized by endothelial cells and is also present in platelets and megakaryocytes.

The essential biologic properties of VWF have been explicated, particularly in the areas of genetic regulation, biosynthesis, and specific bimolecular interactions. The three-dimensional structure of selected domains has been solved, but our understanding of detailed structure-function relationships is still fragmented because of the complexity and size of the VWF molecule. The biomechanical properties of the interaction between the VWF A1 domain and...

TdT (Terminal Deoxynucleotidyl Transferase)

Monday, September 8, 2014 - 15:13

The enzyme family of DNA polymerases plays a fundamental role in the replication, repair, and recombination of nucleic acid. Its members include DNA Polymerase b (Pol b), DNA Polymerase g (Pol g), and DNA Polymerase m (Pol m). TdT is a very unique and fascinating member of this family because, unlike all other DNA polymerases, TdT synthesizes DNA from only single-stranded DNA. This unusual ability to work in a completely template-independent manner was discovered early on (TdT was one of the first activities found in mammals) but not well understood1. An excellent summary of the history, structure, and function of TdT can be found in Motea and Berdis' review2. It is now evident that such random nucleotide addition allows V(D)J recombination and therefore...

RIG-1 - Notorious RIG

Friday, September 5, 2014 - 14:40

Viral infection triggers the antiviral cell response by activating the innate cellular immune system that recognizes various viral components. One component of this process is the cytoplasmic helicase RIG-1 which is a pattern recognition receptor. Like toll-like receptor 3 (TLR3), RIG-1 recognizes double-stranded (ds) RNA, but unlike TLR3, RIG-1 activates tank-binding kinase 1 (TBK1) and inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKepsilon) through the adaptor protein known as interferon-beta promoter stimulator 1 (IPS-1). This kinase cascade ultimately phosphorylates the transcription factors interferon regulatory factors 3 and 7 (IRF-3, IRF-7, respectively). Both of these are essential for type-I interferon expression. Not surprisingly, RIG-1 is required for interferon production in response to RNA viruses (paramyxoviruses, influenza virus, and Japanese encephalitis virus, among...

MUL1 - A Mito's best friend

Thursday, September 4, 2014 - 15:54

MUL1 is an E3 ubiquitin-protein ligase with a RING finger domain that controls mitochondrial morphology, fragmentation and localization. E3 ubiquitin ligases accept the component ubiquitin from a donor E2 ubiquitin-conjugating directly transfer this ubiquitin to designated targeted substrates. The largest, proteome-wide and site-specific quantitative mapping dataset assessment of endogenous putative ubiquitylation sites and regulation was executed by Wagner’s group in Denmark1.  Their compelling experiments also evaluated crosstalk between ubiquitylation and acetylation modifications using an MUL1 antibody. When overexpressed, MUL1 activates the JNK signal cascade and induces caspase-dependent apoptosis. MUL1 has also been shown to negatively regulate Akt kinase, suppressing cell proliferation and viability2.

SOX-11 seals your fate

Wednesday, September 3, 2014 - 14:40

The SOX-11 transcription factor is a member of the SOX family known to be involved in embryonic development regulation and cell fate determination. The protein acts as a transcriptional regulator and appears to modulate fundamental aspects of normal embryonic nervous system development and tumorigenesis. SOX-11 is not found expressed in adult tissues except for the adult immature neuron. Ek's group in Sweden employed the SOX11 antibody to develop signatures comprised of mantle cell lymphoma (MCL)-associated genes through a comprehensive expression analysis of both normal and malignant B-cells1. These profiles were created to identify diagnostic and therapeutic targets that are efficient, genome-based modalities for this aggressive lymphoid malignancy. Additional studies that surveyed a wider range of lymphomas relied upon SOX11 antibody immunohistochemistry and widened the prognostic value of...

PIM-1: An Important Oncogene in Multiple Cancers

Friday, August 29, 2014 - 14:40

The PIM-1 (proto-oncogene serine/threonine-protein kinase) protein is an epithelial-derived, integral membrane serine protease. This protease forms a complex with the Kunitz-type serine protease inhibitor, HAI-1, and is activated by sphingosine 1-phosphate. PIM-1 cleaves and activates hepatocyte growth factor/scattering factor (HGF) as well as urokinase plasminogen activator (uPA). Such downstream targets implicate this serine protease as an epithelial membrane trigger for a sequential protease cascade. PIM-1 expression is associated with many tumors including breast, colon, prostate, and ovarian. Hematologists at UCLA used the PIM-1 antibody to characterize the physiological effects of ABT-869, a multi-targeted receptor tyrosine kinase inhibitor1. This group found that ABT-869 blocked FMS-like tyrosine kinase 3-internal tandem duplication (FLT3) phosphorylation, induced apoptosis, decreased proliferation,...

APE1: A Multifunctional Protein

Wednesday, August 27, 2014 - 15:37

AP-endonuclease (APE1/Ref-1) is an essential multifunctional protein involved in the repair of oxidative DNA damage as well as in transcriptional regulation in tumor cells. It functions as an apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions, and may also play a role in the epigenetic regulation of gene expression and the protection from granzymes-mediated cellular repair leading to cell death. APE1 is involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs).

Melphalan resistance has been considered one of the major obstacles to improve outcomes in multiple myeloma (MM) therapy. A study using Novus’ APE1 antibody, NB100-116, has shown that the acetylation modification of APE1 is involved in melphalan resistance of MM cells and has also shed light on...

FANCD2: A big component of the DNA repair crew

Monday, August 25, 2014 - 13:49

The genetic disorder known as Fanconi anemia (FANC) is a heterogeneous, autosomal-recessive cancer susceptibility condition characterized by a wide array of symptoms. These include congenital malformations, progressive bone marrow failure, DNA-damage hypersensitivity, and genome instability. The protein FANCD2 is a subunit of the protein complex involved in cellular resistance to DNA cross-linking and DNA synthesis arrest triggered by ionizing radiation (IR). The FANCD2 antibody was used in immunoblotting and immunoprecipitation experiments to better understand how processes such as oxidative stress and damage trigger the formation of a multimeric FANC complex within the nucleus1.

Western Blot: FANCD2 Antibody ...

A Double-Edged Sword: GDF15

Friday, August 22, 2014 - 11:04

Bone morphogenetic proteins such as GDF15 belong to the transforming growth factor-beta (TGFB) family that directs tissue differentiation and maintenance. GDF15 appears to be involved in a variety of physiological processes such as pregnancy, injury and inflammation, and apoptosis. Evidence suggests GDF15 is a marker for metastasis. A Swiss group profiled expression of GDF15 via RT-PCR and immunoblotting with the GDF15 antibody in mouse and human glioma cell lines to better correlate tumor grade with proliferative capability and immunogenicity1. Their data clearly showed that endogenous levels of GDF15 cause proliferation and immune escape of glioma cells. Tabrizi et al performed similar profiling studies with the GDF15 antibody in primary ovarian mucinous carcinomas of the intestine2. Based on their studies, they suggest that current and updated diagnostic criteria and standards...

PCSK9: To neuron or not to neuron

Wednesday, August 20, 2014 - 15:36

PCSK9 (Proprotein convertase subtilisin/kexin type 9) is a member of the proteinase K subfamily of the secretory subtilase family. It is first produced as a soluble zymogen that then undergoes an autocatalytic processing within the endoplasmic reticulum (ER). PCSK9 functions in cholesterol homeostasis as well as cortical neuron differentiation. Mutations in this gene are associated with a third form of autosomal dominant familial hypercholesterolemia (HCHOLA3). Blesa’s group used the PCSK9 antibody to study the prevalence of PCSK9 mutations in autosomal dominant hypercholesterolemia (ADH) within a particular Spanish subpopulation1. There were unable to detect any of the previously described mutations they were looking for within this cohort, but identified a novel mutation responsible for increasing PCSK9 transcription. Dube et al employed the PCSK9 antibody in their gestational diabetes...

PINK1 and its role in Parkinson's disease

Tuesday, August 19, 2014 - 15:29

PINK1 (PTEN induced putative kinase 1) is a mitochondrial serine/threonine kinase which maintains mitochondrial function/integrity, provides protection against mitochondrial dysfunction during cellular stress, potentially by phosphorylating mitochondrial proteins, and is involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). PINK1 and its substrates have been found in the cytosol as well as in different sub-mitochondrial compartments.  According to recent reports, PINK1 may be targeted to OMM (outer mitochondrial membrane) with its kinase domain facing the cytosol, providing a possible explanation for the observed physical interaction with the cytosolic E3 ubiquitin ligase Parkin. PINK1 has been linked to autosomal recessive early onset Parkinson's disease, Alzheimer's disease, dementia, multiple sclerosis, schizophrenia, neuronitis, myeloma ect.

...

NUT - A Protein Coding Gene

Friday, August 15, 2014 - 14:27

The NUT gene is found on chromosome 15q14 and encodes for the NUT protein which is a key component of the RNA polymerase II Mediator complex. This multi-subunit assembly is required for all RNA pol II-dependent transcriptional activation, coordinating both nuclear and mitochondrial gene transcription. The complex also includes pol II, and transcription factors TFIIA-F. It serves as a central scaffold within the pre-initiation complex (PIC) responsible for converting biological stimuli (in the form of transcription factors) into gene expression responses. A good review of Mediator function and influencing factors can be found in Poss et al1.

Immunohistochemistry-Paraffin: NUT Antibody...

Neurofibromatosis Infographic

Thursday, August 14, 2014 - 11:07

Neurofibromatosis (NF) is a genetic disorder caused by mutations in the NF1, NF2 or SMARCB1 genes which lead to tumor growth on nerves throughout the body. Although the tumors are usually benign, they still require chemotherapy to shrink and may become cancerous. Surgery is often attempted as treatment, however tumor placement on sensitive areas such as spinal cord and optic nerve make this option more difficult.

Neurofibromatosis Infographic

Resources

  1. CTF.org 
  2. Mayo Clinic ...

NALP4 - Mediator of Programmed Cell Death

Wednesday, August 13, 2014 - 14:26

The NALP family consists of cytoplasmic proteins within the larger CATERPILLER protein family. There exist in short forms (such as NALP4) and long forms (NALP1). NALP proteins include the apoptosis regulator apoptotic protease activating factor 1 (APAF1) and mammalian NOD-LRR proteins, and are thought to play a role in the inflammation and reproduction processes. They play a key role in the formation of large signal-induced proinflammatory multiprotein complexes termed "inflammasomes", as published in a Nature Molecular Cell Biology 2003 review by Tschopp, more recently reviewed by Boaru1,2. NALP4 is also involved in modulating NF-kB activity.

MDA5 - Part of the RIG-I-like Receptor Family

Monday, August 11, 2014 - 14:34

The innate immune system is responsible for reacting to viral infections through recognition of various viral components. Like toll-like receptor 3 (TLR3), MDA5 recognizes double-stranded (ds) RNA which is a molecular pattern indicative of viral infection. MDA5 and its relative RIG-1 recognize different types of dsRNA, with MDA5 recognizing poly (I:C). MDA5 is a member of the DEAD/DEAH-box RNA helicase family, which all contain the conserved DEAD motif of Asp-Glu-Ala-Asp. DEAD box proteins are implicated in a number of cellular processes involving RNA secondary structure alteration - translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. When stimulated by dsRNA, MDA5 recruits the adaptor protein VISA and ultimately activates...

Mannose 6 Phosphate Receptor: Once you're tagged, there's no going back!

Thursday, August 7, 2014 - 13:57

Mannose 6 phosphate (M6P) is a sequence tag that plays a pivotal role in transporting proteins from the Golgi complex and cell surface to the lysosome. The M6P sequence is tagged to the N-linked oligosaccharides of lysosomal hydrolases as they traverse the cis-Golgi apparatus. Upon M6P-tagging, these proteins are targeted to the late endosome via vesicular transport. Low pH conditions there mediate the dissociation of a M6P Receptor from its ligand, allowing recycling of the M6P sequences. Furthermore, M6P is bound by lectin in the immune system, and is converted to fructose 6-phosphate by mannose phosphate isomerase.

iNOS: The Nitric Oxide Boss

Wednesday, August 6, 2014 - 15:35

Nitric oxide (NO) is an inorganic, gaseous, and reactive free radical that acts as a biologic mediator in processes such as neurotransmission, vasorelaxation, and cytotoxicity. In addition, it has antimicrobial and anti-tumoral activities. NO production is mediated by members of the nitric oxide synthase (NOS) family. The NOS enzyme catalyzes the oxidization of L-arginine into L-citrulline and NO.  Several subtypes have been identified: two constitutive isoforms (type I brain/neuronal NOS, and type III endothelial) and one inducible isoform (iNOS, or type II).

Immunohistochemistry-Paraffin: iNOS Antibody Immunohistochemistry-Paraffin: iNOS Antibody

iNOS is found in a variety of cell types including macrophages, hepatocytes, synoviocytes, and...

Interleukin 6 (IL-6) - I can change your body's temperature set point!

Tuesday, August 5, 2014 - 15:13

IL-6 is an immunoregulatory cytokine that functions in inflammation and B-cell maturation. It was originally identified as a B-cell differentiation factor. It is primarily made at sites of acute and chronic inflammation, where it is secreted into serum and induces a transcriptional inflammatory response through the cell surface assembly of interleukin-6 alpha receptor (IL-6R, alpha) and the signaling receptor gp130. IL-6 functions in a large and wide variety of inflammation-associated disease states, including fever and the acute phase response, energy mobilization, innate immunity response, and susceptibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Rincon and Irvin give a thorough overview of the role of IL-6 in asthma and pulmonary inflammatory diseases1. Additionally, IL-6 functions in the...

ABCA1 - The Caretaker for Cholesterol Transportation

Monday, August 4, 2014 - 15:41

The ATP-binding cassette transporter A1 (ABCA1) protein is a key gatekeeper for regulating intracellular cholesterol transport. It is one member of a large family of genes comprised of cAMP-dependent anion transporter cell membrane proteins. These important proteins regulate reverse cholesterol efflux from cells into the peripheral tissues via apolipoprotein A-1 (apo). ABCA1 in particular has a diverse expression profile and is most highly expressed in macrophages. Sporstol's group performed real-time RT-PCR and immunoblotting with the ABCA1 antibody to create detailed expression pattern profiles of their identified cholesterol metabolism targets (scavenger receptor type B class I (SR-BI), ABCA1, and ABC transporter G1 (ABCG1) proteins)1. A research group from the Cornell Medical Center used the ABCA1...

CD11b - More than a microglial marker

Wednesday, July 30, 2014 - 12:38

The protein CD11b has been implicated in the various adhesion-related interactions of cells such as monocytes, macrophages, natural killer (NK) cells, and granulocytes. It is part of a heterodimer that consists of CD11b and CD18. It also modulates the uptake of complement-coated particles within the cell. It is commonly used as a microglial marker in tissues derived from the nervous system. Immunoblotting experiments with the CD11b antibody from Wong’s lab indicate that hypoxia-inducible factor 1 (HIF-1) critically regulates breast cancer metastases by priming the lung niche microenvironment before the arrival of secondary tumor cells1. The same group used the CD11b antibody in their follow-up studies where they monitored the effects of two distinct HIF inhibitors – digoxin and acriflavine – on niche formation2...

Amyotrophic Lateral Sclerosis Infographic

Tuesday, July 29, 2014 - 11:27

Amyotrophic lateral sclerosis is a neurological disease which impacts motor neurons that are involved in muscle movement throughout the body. The progressive degeneration of neurons causes weakened muscles and can lead to paralysis. There is no cure for ALS, but riluzole has been used to help with the damage to the motor neurons.

AMYOTROPHIC LATERAL SCLEROSIS (ALS)

 

Resources:

  1. ALSA.org 
  2. Lougehrig.com 
  3. ...

HIF-1 beta: A Dimerization Partner of HIF-1 alpha Required for an Adaptive Response to Hypoxia

Monday, July 28, 2014 - 14:21

Hypoxia contributes significantly to the pathophysiology of major categories of human disease, including myocardial and cerebral ischemia, cancer, pulmonary hypertension, congenital heart disease and chronic obstructive pulmonary disease. Hypoxia-inducible factor 1 (HIF-1) is a nuclear protein involved in mammalian oxygen homeostasis. It is a heterodimer composed of HIF-1 alpha and HIF-1 beta subunits which are bHLH proteins of PAS (PER, ARNT, SIM) family. HIF-1 beta forms heterodimer with AHR, AHRR, HIF1 alpha and EPAS1/HIF2 alpha as well as with other bHLH proteins and its dimerization is required for efficient DNA binding.

HIF-1 beta is encoded by the ARNT (Aryl Hydrocarbon Receptor Nuclear...

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