Archive for the ‘Antibody database’ Category

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Cancer studies with ABCF2

Wednesday, February 8th, 2012

ATP-binding cassette superfamily F2 (ABCF2) is a member of the ATP-binding cassette (ABC) transporter superfamily, and more specifically, a member of the GCN20 subfamily. Most members of this family are membrane proteins that transport various substrates across the cell membrane [1, 2]. ABC genes have a pair of nucleotide binding folds (NBF) and trans-membrane (TM) domains; ABCF2 differs by having a pair of NBF’s but no TM domains.  It is this distinction that leads most researchers to believe that ABCF2 does not have any membrane transport function, but instead may be involved in translational control, antibiotic resistance, and RNase L inhibition [1, 3].

Areas of study that utilize the ABCF2 protein include breast cancer, cervical cancer, clear cell ovarian adenocarcinoma, and endometrial cancer.  Studies have found that ABCF2 may play a role in tumor suppression at metastatic sites, the endocrine pathway for breast cancer, and as a useful biomarker for cervical cancer [2, 3, 4].  Some breast cancers, being endocrine dependent cancers, utilize hormones for carcinogenesis.  ABCF2 expression has been seen to increase in these types of breast cancer tissues. This suggests that ABCF2 may act as a surrogate marker for endocrine dependent proteins.  There is also evidence that there is a relationship between ABCF2 expression and sensitivity to endocrine therapy [2].

The overexpression of ABCF2 was also found in conjunction with ectopic endometriosis [2].  However, ABCF2 expression is not related to prognosis or clinical factors such as age, stage, histologic type, histologic grade, and estrogen receptor status in endometrial cancer [3].

In cervical cancer, ABCF2 expression is found to be higher in stages III and IV.  Currently, squamous cell antigen (SCC) is used as a marker for cervical cancer; however, there are conflicting reports on the accuracy of pretreatment SCC measurements as it pertains to prognostic significance [3].   In cervical non-squamous cell carcinoma, ABCF2 expression is prevalent.  This ABCF2 expression correlated with overall survival in clinical trials.  ABCF2 may therefore be a more useful biomarker for cervical non-squamous cell carcinoma [3].

  1. Dean, M., Rzhetsky, A., and Allikmets, R. 2001. The Human ATP-Binding Cassette [ABC] Transporter Superfamily. Genome Research. 11: 1156-1166.
  2. Hiroshi, T., Ito, Y.M., Ohashi, Y., Wong, K., Hashinguchi, Y., Welch, W., Berkowitz, R.S., Birrer, M.J., and Mok, S.C. 2005. Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray analyses.  Clin Cancer Res. 11: 6880.
  3. Nishimura, S., Tsuda, H., Miyagi, Y., Hirasawa, A., Suzuki, A., Kataoka, F., Nomura, H., Chiyoda, T., Banno, K., Fujii, T., Susumu, N., and Aoki, D. 2008. Can ABCF2 protein expression predict the prognosis of uterine cancer? British Journal of Cancer. 99: 1651-1655.
  4. Ogawa, Y., Tsuda, H., Hai, E., Tsuji, N., Yamahgata, S., Tokunaga, S., Nakazawa, K., Tamamori, Y., Ogawa, M., Shimizu, S., Inoue, T., and Nishiguchi, Y. 2006. Clinical role of ABCF2 expression in breast cancer. Anticancer Research. 26: 1809-1814.

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BSP and Osteopontin Antibodies: A Case of SIBLING Rivalry?

Thursday, February 2nd, 2012

Bone and dentin are closely related tissues, formed when a type I collagen-rich extracellular matrix (ECM) is secreted from the osteoblasts or odontoblasts and subsequently mineralized. This process is tightly regulated by type I collagen plus a number of non-collagenous proteins, including members of the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family. Antibodies associated with this group include the Dentin Matrix Protein 1 (DMP1), Dentin Sialophosphoprotein (DSPP), Bone Sialoprotein (BSP) and Osteopontin (OPN).

The newest member of the family is Matrix Extracellular Phosphoglycoprotein (MEPE), of which presently little is known. However BSP, DSPP, DMP1 and OPN antibody studies suggest the proteins regulate crystal growth and mineralization of collagen fibers within the ECM during its conversion to bone or dentin.

Osteopontin antibody assays suggest little similarity between the amino acid sequence of OPN and those of its relatives. Nonetheless, the SIBLING proteins do share a number of common features, including an Arg-Gly-Asp (RGD) motif which binds to cell-surface integrins, allowing cell attachment and signalling. The RGD tri-peptide is always located on the last one or two exons (which are the largest) and all the SIBLING genes occupy a common chromosome location: 4q21-23. Finally, recent studies with SIBLING family antibodies have shown the proteins undergo a number of similar post-translational modifications, including phosphorylation, sulfuration, glycosylation, transglutaminase cross-linking and proteolytic processing.

Many of the mechanisms controlling bone and dentin synthesis remain elusive, but BSP and osteopontin antibody assays clearly show a link between SIBLING protein activity and PTMs, which must alter the structure and therefore function of the proteins in the same way histone modifications do.

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Caspase 3/7 Inhibitors Show Potential for Anti-Inflammatory Therapies

Wednesday, February 1st, 2012

Apoptosis is one of the best-characterized phenomena in cellular and molecular biology. Not only is it essential for successful development, but its deregulation also leads to a number of human diseases, most notably cancer. The cysteine aspartate protease (caspase) family of proteins has been studied extensively over the past several decades and found to play a pivotal role in the execution of apoptosis; caspase activation is regarded as commitment to programmed cell death.  A variety of intrinsic and extrinsic stressors are capable of initiating mediated cell death, however, transduction commonly occurs via caspase activity.  Initiator caspases (8, 9, 10 and 2) are activated first, generally by binding oligomeric adaptor proteins, and subsequently activate the effector caspases (3, 7 and 6) via proteolytic cleavage.

Recent research has revealed a novel role for caspases, notably caspase-8 and -3/7, in mediating neurotoxicity in response to inflammatory stimuli in microglia.  Although microglia are the primary effectors of the immune response in the nervous system, numerous studies suggest that their aberrant activation contributes to neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s and multiple sclerosis.  In their groundbreaking research, Burgillos, et al. show that exposure of microglia to pro-inflammatory cytokines leads to activation of caspase-3/7 and neurotoxicity associated with neurological disease.  Surprisingly, they also demonstrated that inhibition of caspase-3/7 inhibited microglial activation, and that lipopolysaccharides failed to damage neighboring neurons when caspase-3/7 was abrogated chemically or with siRNA.  Finally, they provide evidence that the IKK/NF-kB pathway—a canonical pro-inflammatory pathway– is also influenced by caspase-3/7 by their ability to trigger PKC-delta.

Neuronal inflammation is both a prominent cause and result of brain injury and the identification of caspase-3/7 and -8 in its etiology provides exciting new targets for potential therapies.  Coupled with the advent of nano-carriers capable of traversing the blood brain barrier, caspase-3/7 could be promising substrates for novel anti-inflammatory drugs.  Novus Biologicals provides several excellent antibodies to target caspase-3 and -7 (such as NB500-206 and NB500-210) that we hope will accelerate research in this field.  We are committed to producing quality research materials, and look forward to learning how our caspase 3 and caspase 7 antibodies will serve the scientific community.

Burgillos MA, Deierborg T, Kavanagh E, et al.  Caspase signaling controls microglia activation and neurotoxicity.  Nature 2011; 472:319-324.

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Breast Cancer and RAD51L1 Antibodies

Friday, January 27th, 2012

In the United States, breast cancer is one of the most common cancers and the second leading cause of cancer related deaths in women. According to the American Cancer Society’s most recent estimates for breast cancer in the United States, there are about 200,000 new cases of invasive breast cancer, 60,000 new cases of carcinoma in situ (CIS),  and approximately 40,000 deaths from breast cancer this year.

A predisposition to breast and ovarian cancer has been linked to mutations in the BRCA1 and BRCA2 genes.  In cells where the BRCA1 and BRCA2 genes are defective, there are indications of gross chromosomal rearrangements and breakage.  Antibody studies have shown that the RAD51L1 protein specifically targets and fixes double stranded DNA breaks, which are the main cause of the genomic instability in these cells, via the RAD51-mediated DNA repair system (PMID: 15065660).

RAD51L1 also known as DNA repair protein RAD51 homolog 2, RAD51 homolog B, RAD51-like protein 1, RAD51L1, RAD51B, REC2, and R51H2, is a member of the RAD51 protein family and is involved in the early stages of the homologous recombination repair pathway.  Homologous recombination occurs before the cell enters mitosis; during and shortly after DNA replication when sister chromatids are present.  The 5’ end of the damaged DNA molecule is cut away and the open 3’ end, where RAD51L1 binds and forms a helical nucleoprotein filament, then invades a similar or identical portion of an another intact DNA molecule (PMID: 19329439).  BRCA1 and BRCA2 work in conjunction with the RAD51 paralogues (RAD51C, RAD51D, XRCC2, and XRCC3), and some recombination proteins (RAD52, RAD54, RPA, and EVL) to create the RAD51L1 helical nucleoprotein filament (PMID: 19329439, PMID: 15065660). Studies have found that cells with defective BRCA genes fail to create RAD51L1 filaments, and therefore have a lowered cellular repair capacity that can lead to complications such as unregulated cell division and the formation of cancerous tumors (PMID: 15065660, PMID: 20610542).

Please see our website for antibodies, proteins and other reagents related to RAD51L1, homologous recombination, BRCA1, and BRCA2, or contact our technical support department (technical@novusbio.com) for additional details.

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S100A6: Playing Roles in Cancer, Apoptosis & Transcription Regulation

Thursday, January 26th, 2012

S100A6 antibodies detect a small calcium binding protein with 2 EF-hand structures and belongs to the S100 family. Calcium binding induces a conformational change of the protein which in turn permits its interaction with several target proteins. It is predominantly expressed in fibroblasts and epithelial cells and has been implicated in several cellular processes such as cell cycle progression, cytoskeleton rearrangement and exocytosis. It is a predominantly cytoplasmic protein however in the presence of calcium ions it might also associate with cell membranes.  Its vast array of biological processes may be due to the fact that it has the ability to bind a number of proteins and modulate their function by inducing conformation changes and/or interfering with post-translational modifications.

The upregulation of S100A6 has been reported in a number of tumors and linked to metastasis.  Recent studies have demonstrated a strong link between high nuclear expression of S100A6 and poor survival in pancreatic cancer patients.  It was concluded that up-regulation of S100A6 is an early event in pancreatic cancer development and that elevated levels of nuclear S100A6 influence the clinical outcome.

S100A6 has also been linked to apoptosis.  It has been shown to enhance the cell death rate of cells under apoptotic conditions when upregulated.  This is believed to be due to the interaction between S100A6 and Caspase 3 during which S100A6 is thought to modulate the transcriptional regulation of caspase 3 by increasing its promoter activity.

P53 appears to be another protein which S100A6 interacts with.  The presence of S100A6 results in higher p53 transcriptional activity which resulted in a higher cell susceptibility to apoptosis induced by hydrogen peroxide.  The binding of S100A6 to p53 did not however affect the ability of p53 to bind to DNA.

As S100A6 is further studies, more protein binding partners are bound to be discovered.  This may shed more light on the diverse roles that S100A6 plays in a vast array of cellular processes. Novus offers top quality S100A6 antibodies as well as lysates, recombinant proteins, RNAi and many other support reagents. Please contact our technical support department (technical@novusbio.com) for any additional details.

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LXR Alpha, ABCA1 and Cholesterol Homeostasis

Friday, January 20th, 2012

LXR Alpha, also known as Liver X receptor Alpha is a 50KDa protein that belongs to the nuclear hormone receptor family located in the nucleus. It is specifically expressed in the liver, kidney and intestine; however it has also been found in the spleen, macrophages and the adrenals. All of these tissues play an important role in lipid metabolism. The primary role of LXR Alpha is to maintain cholesterol homeostasis in macrophages by regulating the genes involved in this. LXR Alpha activates the ABCA1 gene in macrophages which results in an increased movement of cholesterol to High-density Lipoproteins. The activation of the ABCA1 gene results in conditions such as atherosclerosis where there is an accumulation of cholesterol in the arteries. Macrophages which are present in this accumulation have the ability to gather oxysterols which then activate the LXR genes. The LXR genes then activate the ABCA1 gene. LXR Alpha is also known to enhance the expression of the inflammatory genes MCP1 and MCP2 along with many chemokines and cytokines. Not only does LXR Alpha play an important role in cholesterol homeostasis in the arteries but it also plays an important role in cholesterol homeostasis in Oligodendrocytes.

Here at Novus Biologicals, we have a wide range of LXR Alpha Antibodies that have been validated for most species and applications. They have all been thoroughly tested and we have some excellent validation data images on our datasheets. Please contact technical@novusbio.com with any questions about these or any other Novus reagents.

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MAT2a, MAT2b, HIF-1 alpha: Roles in Liver Cancer and DNA methylation

Thursday, January 19th, 2012

Methionine Adenosyltransferase II alpha, also known as MAT2a, is a catalytic subunit of methionine adenosyltransferase (MAT) and essential enzyme for the catalysis of the principle biological methyl donor, S-adenosylmethionine (SAM) from methionine and ATP. MAT2a’s heterotetramer structure is composed of 2 catalytic alpha subunits (alpha and alpha’)1. During development in the adult human liver, MAT2a and its gene products are progressively replaced by MAT1a during fetal liver development2. Increased growth and malignant degenerations has been observed in hepatocytes expressing increased levels of MAT2a and MAT2b2. It has been frequently observed in malignant liver transformation, that the expression of MAT1a is switched to MAT2a, which is believed to be an important factor in facilitating liver cancer progression3.

Recent studies have been conducted to investigate the potential interaction between MAT2a and HIF-1a as a mechanism being responsible for the change in genomic DNA methylation patterns found in liver cancer under hypoxic conditions. MAT2a was identified as a novel target gene that is transcriptionally regulated by HIF-1a. This provided the evidence needed to support that genomic DNA methylation is regulated by activation of HIF-1a and the up-regulation of MAT2a in hepatoma cells under hypoxic conditions3. Western blot and luciferase analysis in this study revealed a positive correlation between HIF-1a and MAT2a promoter activity expression in Hep3B cells after Hypoxic treatment. The use of siRNA to knockdown HIF-1a was shown to prevent the expression of MAT2a.  Furthermore, ChIP analysis revealed a significant increase in the binding of HIF-1a to the MAT2a promoter within hypoxic Hep3B cells3. The results from this study suggest that genomic DNA methylation is facilitated by the activated expression of MAT2a through HIF-1a under hypoxic conditions, due to the increase of MAT II activity and decrease of SAM production.

Novus offers many different MAT2a and HIF-1a antibodies to for your research needs. All Novus Products are covered by Novus’ 100% guarantee. Please feel free to contact our technical support staff for more information about the antibodies, proteins, lysates and other products that we carry.

References:

1. Wang Q, Liu Q, Liu Z, Qian Q, Sun Q and Pan D. Inhibition of hepatocellular carcinoma MAT2A and MAT2beta gene expressions by single and dual small interfering RNA. Journal of Experimental & Clinical Cancer Research 2008. 27:72. [PMID: 19025580]

2. Chen H, Xia M, Lin M, Yang H, Kuhlenkamp J, Li T, Sodir NM, Chen YH, Josef-Lenz H, Laird P, Clarke S, Mato J, and Lu S.  Role of Methionine Adenosyltransferase 2A and S—adenosylmethionin in Mitogen-Induced Growth of Human Colon Cancer Cells. Gastroenterology 2007; 133:207-218. [PMID: 17631143]

3. Liu Q, Liu L, Zhao Y, Zhang J, Wang D, Chen J, He Y, Wu J, Zhang Z, and Liu Z. Hypoxia Induces Genomic DNA Demethylation through the activation of HIF-1a and Transcriptional Upregulation of MAT2A in Heptoma Cells. Molecular Cancer Therapeutics 2011;10:1113-1123. [PMID: 21460102]

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Vimentin Antibodies in Rheumatoid Arthritis & Cataracts Research

Wednesday, January 18th, 2012

Vimentin is a 57kDa type III intermediate filament (IF) protein that is the major cytoskeletal component of mesenchymal cells and the first to be expressed during cell differentiation. It plays a significant role in supporting and anchoring the position of the organelles in the cytosol and its dynamic nature is important for cell flexibility.  It is responsible for maintaining cell shape and cytoplasm integrity.

Vimentin has been implicated in a number of diseases.  It is frequently included in the primary panel of markers in the identification of mesenchymal tumors and malignant melanomas.  Some of the other markers used in that panel are CD45, cytokeratin and S-100 protein.

Antibodies against mutated and citrullinated Vimentin have become the forefront of Rheumatoid Arthritis (RA) recognition and diagnosis.  RA is a disorder which is difficult to recognize in the early period of disease manifestation.  There are 2 types of serological markers which are used for the diagnosis of RA:  antibodies to the Fc part of human IgG (rheumatoid factor) and antibodies to citrullinated protein/peptide antigens.  Antibodies against citrullinated Vimentin provide high specificity for the diagnosis of RA and have now been developed into a novel and rapid test system (American College of Rheumatology, 2008 Annual Scientific Meeting).

Vimentin has also been shown to play a key role in maintaining eye lens integrity.  A mutation, G596A substitution on exon 1, has been shown to cause an assembly defect in Vimentin which lead to cause cataract in the human patient.  The mutated vimentin formed an abnormal Vimentin cytoskeleton and caused an increase in the proteasome activity of transfected cells (Muller et al, 2009. Human Molecular Genetics).

Taken in summary, Vimentin and its implications in disease invite novel therapy approaches in the areas of cancer, rheumatoid arthritis and cataracts.  Novus Biologicals is at the forefront of the scientific research involved in these diseases and offers an impressive array of Vimentin antibodies and support reagents.

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Breast Cancer and RAD51L1 Antibodies

Friday, January 13th, 2012

In the United States, breast cancer is one of the most common cancers and the second leading cause of cancer related deaths in women. According to the American Cancer Societ’s most recent estimates for breast cancer in the United States, there are about 200,000 new cases of invasive breast cancer, 60,000 new cases of carcinoma in situ (CIS),  and approximately 40,000 deaths from breast cancer this year (2).

A predisposition to breast and ovarian cancer has been linked to mutations in the BRCA1 and BRCA2 genes.  In cells where the BRCA1 and BRCA2 genes are defective, there are indications of gross chromosomal rearrangements and breakage.  The RAD51L1 protein specifically targets and fixes double stranded DNA breaks, which are the main cause of the genomic instability in these cells, via the RAD51-mediated DNA repair system  (PMID: 15065660).

RAD51L1 also known as DNA repair protein RAD51 homolog 2, RAD51 homolog B, RAD51-like protein 1, RAD51L1, RAD51B, REC2, and R51H2, is a member of the RAD51 protein family and is involved in the early stages of the homologous recombination repair (HRR) pathway.  Homologous recombination (HR) occurs before the cell enters mitosis; during and shortly after DNA replication when sister chromatids are present.  The 5’ end of the damaged DNA molecule is cut away and the open 3’ end, where RAD51L1 binds and forms a helical nucleoprotein filament, then invades a similar or identical portion of an another intact DNA molecule (PMID: 19329439).  BRCA1 and BRCA2 work in conjunction with the RAD51 paralogues (RAD51C, RAD51D, XRCC2, and XRCC3), and some recombination proteins (RAD52, RAD54, RPA, and EVL) to create the RAD51L1 helical nucleoprotein filament (PMID: 19329439, PMID: 15065660). Studies have found that cells with defective BRCA genes fail to create RAD51L1 filaments, and therefore have a lowered cellular repair capacity that can lead to complications such as unregulated cell division and the formation of cancerous tumors (PMID: 15065660, PMID: 20610542).

Please see our website for products related to RAD51L1, homologous recombination, BRCA1, and BRCA2 antibodies, proteins and other reagents.

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Can Tubby make you Tubby?

Thursday, January 12th, 2012

The TUB gene, which encodes for the protein Tubby, is evolutionarily conserved in human, chimpanzee, dog, cow, mouse, chicken, zebrafish, fruit fly, mosquito, C.elegans, and rice.

The gene derives its name from its role in metabolism; mice with a mutated tubby gene develop delayed-onset obesity, sensorineural hearing loss and retinal degeneration (a syndrome known as the autosomal recessive syndrome “Tubby”)

The first tubby gene was identified in mice, and proteins that are homologous to tubby are known as “tubby-like proteins” (TULPs).

The identification of a mutation at the tubby (Tub) locus in mice, led to the discovery of the homologous tubby-like proteins (TULPs). Tub and the genes that encode for TULPs (TULP1, TULP2, TULP3, and TULP4) form a novel, small gene family that plays an important role in maintenance and function of neuronal cells during development and post-differentiation.

All TULPs including TUB are classified as alpha and beta proteins and they share a common and characteristic tertiary structure that consists of a 12-beta stranded barrel packed around an alpha helix in the central pore.

The tubby protein is an upstream cell signaling protein common to multicellular eukaryotes which can bind the small cell signaling molecule phosphatidylinositol, which is typically localized to the cell membrane.

So can Tubby really make you Tubby?

The tubby protein is highly expressed in brain, especially hypothalamus where body weight regulation is controlled. The sequence of normal tubby includes putative tyrosine phosphorylation sites for SH-2 protein binding and a nuclear localization signal, while mutant tubby contains a 24 intron amino-acid insert substituted for 44 C-terminal amino acids.  In PC12 cells, insulin induces tyrosine phosphorylation. In vitro, tubby is phosphorylated by insulin receptor kinase, Abl, JAK2; and upon phosphorylation, tubby associates with the SH2 domains of Abl, Lck, phospholipase Cγ. The C-term region of tubby binds to phosphatidylinositol 4,5-bis-phosphate, which facilitates localization to the plasma membrane.  Receptor-mediated activation of Gαq releases tubby from the plasma membrane through the action of phospholipase C-B. This allows translocation of tubby to the nucleus where it plays a role in regulating transcription. Tubby proteins are also associated with neuronal differentiation and development, and when mutated, in mammals we observe obesity, retinal degeneration, and hearing loss.  In mice, mutations in tubby proteins are also known to affect life span and fat storage as well as carbohydrate metabolism.

Novus offers high quality Tubby antibodies for use on human or C. elegans in Western blot and immunostaining, as well as recombinant protein and RNAi controls.

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