Autophagy Pathway

New Discoveries on Autophagy Impaired clearance of dying cells has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). A noncanonical autophagy pathway is known to engage LC3-associated phagocytosis (LAP), where autophagy elements are recruited to facilitate phagosomal maturation for cellular clearance. A new study discovers that the defects in noncanonical LAP, but not canonical autophagy, cause SLE-related pathology in mice. (Nature, 2016) Autophagy is a highly conserved cellular process. While the cytoplasmic components of autophagy have been progressively unveiled, transcriptional and epigenetic regulation of autophagy is poorly understood. The new findings demonstrate that the histone arginine methyltransferase CARM1 acts a critical co-activator of TFEB to initiate autophagy-related gene expression and that autophagy induction can be regulated by the AMPK-SKP2-CARM1 signaling axis, in response to cellular starvation. (Nature, 2016) Urolithins are metabolites of ellagitannins found in the pomegranate, nuts and berries. In this novel discovery, urolithins are found to improve fitness and extend lifespan of C. elegans. Urolithin A (UA) induces autophagy of mitochondria (mitophagy) and prevents accumulation of dysfunctional mitochondria. In rodents, UA improves the exercise capacity through mitophagy induction. These findings propose the medicinal potential of UA for improving mitochondrial and muscular function. (Nature Medicine, 2016) Autophagy Dysregulation: Diseases and Genes Condition Disease Genes Neurodegeneration Alzheimer's disease BECN1, PSEN1, APOE, APP, SNCA, ATP13A2 Parkinson's disease PARK2, PARK6 Huntington's disease HTT Inflammation Chrohn's disease ATG16L1, NOD2, IRGM Ulcerative colitis SMURF1 Malignancy Ovarian and prostate cancer BECN1 Colon cancer UVRAG, PARK2 Lung and brain cancer PARK2 Breast cancer BECN1, EI24/PIG8 Immune disorder Systemic lupus erythematosus ATG5 Childhood and adult asthma ATG5 Infection Tuberculosis IRGM   Mammalian Authophagy (Macroautophagy) Pathway (Click to see your products of interest) Eight Product Categories and 1500+ Products 385 Monoclonal Antibodies 602 Polyclonal Antibodies 202 Antibody Pairs 171 Recombinant Proteins 44 ELISA and Assay Kits 110 RNAi 17 FISH Probes 64 Cell Transient Overexpression Lysates Featured Products MTOR monoclonal antibody (M01), clone 2C5 H00002475-M01 Proximity Ligation Analysis of protein-protein interactions between AKT1 and MTOR. HeLa cells were stained with anti-AKT1 (H00000207-D01P) rabbit purified polyclonal (1:1200) and anti-MTOR mouse monoclonal antibody (1:50). Each red dot represents the detection of protein-protein interaction complex, and nuclei were counterstained with DAPI (blue). SQSTM1 monoclonal antibody (M01), clone 2C11 H00007474-M04 Immunofluorescence of monoclonal antibody to SQSTM1 on HeLa cell. [antibody concentration 10 ug/ml]. PRKAA2 monoclonal antibody (M02), clone 1G8 H00005563-M02 Proximity Ligation Analysis of protein-protein interactions between STK11 (H00006794 – D01P) and PRKAA2. HeLa cells were stained with anti-STK11 rabbit purified polyclonal (1:1200) and anti-PRKAA2 mouse monoclonal antibody (1:50). Each red dot represents the detection of protein-protein interaction complex, and nuclei were counterstained with DAPI (blue). References Jennifer Martinez, et al. (2016) Nature. DOI: 10.1038/nature17950 Hi-Jai R Shin, et al. (2016) Nature. DOI:10.1038/nature18014 Dongryeol Ryu, et al. (2016). Nature Medicine. DOI: 10.1038/nm.4132 Peidu Jiang, et al. (2014). Cell Research. DOI: 10.1038/cr.2013.161 Ralph A Nixon, et al. (2013). Nature Medicine. DOI: 10.1038/nm.3232 Augustine M.K. Choi, et al. (2013). The New England Journal of Medicine. DOI: 10.1056/NEJMral205406 New Products   200+ New Mouse Monoclonal Antibodies to empower your research

Wnt/β-catenin Signaling Pathway

New Discoveries on Wnt/β-catenin Signaling Pathway PolyADP-ribose polymerase Tankyrase plays a key role in oncogenic Wnt/β-catenin signaling pathway. This study unveils that in addition to facilitating cytosolic β-catenin accumulation, the polymerization of TNKS and TNKS2 sterile alpha motif domains is also essential to drive oncogenic gene transcription. (Molecular Cell, 2016) New mechanism of action for axitinib, a clinically approved tyrosine kinase inhibitor for treating renal cell carcinoma, is demonstrated here. Axitinib is shown to directly target and stabilize SHPRH, an E3 ubiquitin ligase. In doing so, axitinib blocks Wnt/β-catenin signaling pathway by increasing nuclear β-catenin ubiquitination and degradation, and ultimately promotes asymmetric cell division in cancer cells. (PNAS, 2016) New therapeutic aspects in treating chemoresistant cancer are proposed. Due to the common upregulation of O6-methylguanine-DNA methyltransferase (MGMT) in patients developing chemoresistance, this study demonstrates that successful inhibition of Wnt/β-catenin signaling downregulates expression of MGMT and restores chemosensitivity. (Nature Communications, 2015) Wnt/β-catenin Signaling Pathway (Click to see your products of interest) Eight Product Categories and 1700+ Products 428 Monoclonal Antibodies 594 Polyclonal Antibodies 177 Antibody Pairs 236 Recombinant Proteins 46 ELISA and Assay Kits 158 RNAi 35 FISH Probes 70 Cell Transient Overexpression Lysates Featured Products CTNNB1 monoclonal antibody (M02), clone 1C9 H00001499-M02 Immunofluorescence staining of HeLa cells with CTNNB1 monoclonal antibody, clone1C9 (Cat. #H00001499-M02) at 10 ug/ml. WNT5A monoclonal antibody (M04), clone 3A4 H00007474-M04 Immunohistochemistry staining of formalin-fixed paraffin-embedded human placenta with WNT5A monoclonal antibody, clone 3A4 (Cat. # H00007474-M04) at 3 ug/ml. MYC (Orange) FISH Probe FG0099 Fluorescent in situ hybridization of MYC FISH probe in human cell lines (Cat. # FG0099). Corresponding images of hybridization results in a low copy-number MYC expressing HL60S cell line (left) and high copy-number MYC expressing NCiN417 cell line (right). References Laura Mariotti et. al. (2016) Molecular Cell, DOI:10.1016/j.molcel.2016.06.019 Malin Wickström, et. al. (2015) Nature Communications. DOI:10.1038/ncomms9904 Yi Qu, et. al. (2016). PNAS. DOI: 10.1073/pnas.1604520113 New Products   200+ New Mouse Monoclonal Antibodies to empower your research

Lysosomal Regulations

New Discoveries on Lysosomal Regulations Related Research A mechanism in phagocytosis involving TFEB-dependent Fcγ-receptor activation was found to enhance lysosomal degradation. The results of this study suggest that phagosomes and lysosomes are capable of bi-directional signaling. (Cell Current Biology, 2016) Motility is crucial for lysosomes to traffic towards cargo-carrying vesicles for the degradation of biomacromolecules. Here, the release of Ca2+ through lysosomal Ca2+ channel TRPML1 was found to regulate lysosome motility, positioning and tubulation. (Nature Cell Biology, 2016) Results of this study unveiled a lysosomal response to the arrival of autophagosomal cargo in which OCRL plays a key role. Depleting or inhibiting OCRL leads to an accumulation of lysosomal PtdIns(4,5)P2, an inhibitor of the calcium channel mucolipin-1 that controls autophagosome–lysosome fusion. (Nature Cell Biology, 2016) Lysosomal Membrane Proteins and Diseases   Gene Name   Gene ID   Gene Mutation Related Diseases   CLCN7   1186   Malignant infantile osteopetrosis   CLN3   1201   Juvenile neuronal ceroid lipofuscinosis   CTNS   1497   Cystinosis   HGSNAT   138050   Mucopolysaccharidosis type IIIC   LAMP2   3920   Danon disease   LMBRD1   55788   Cobalamin F-type disease   MCOLN1   57192   Mucolipidosis type IV   MFSD8   256471   Late infantile neuronal ceroid lipofuscinosis   NPC1   4864   Nemann-Pick type C   OSTM1   28962   Malignant infantile osteopetrosis   SCARB2   950   Action myoclonus-renal failure syndrome   SLC17A5   26503   Salla disease Lysosomal Regulations (Click to see your products of interest)

Eight Product Categories and 200+ Products
63 Monoclonal Antibodies 49 Polyclonal Antibodies 2 Antibody Pairs 45 Recombinant Proteins	1 ELISA and Assay Kits 36 RNAi 2 FISH Probes 15 Cell Transient Overexpression Lysates

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CD63 monoclonal antibody, clone MEM-259 (PerCP) MAB6493

Immunofluorescence staining of human primary fibroblasts with CD63 monoclonal antibody, clone MEM-259 (Cat # MAB6493, green) after co-incubation of living cells with human Transferrin-Dyomics 547 (red) . Cell nuclei stained with DAPI (blue).

ATP6V1A monoclonal antibody (M02), clone 4F5
H00000523-M02

Immunohistochemistry staining of formalin-fixed paraffin-embedded human placenta with ATP6V1A monoclonal antibody (M02), clone 4F5 (Cat # H00000523-M02) at 3 ug/mL.

LAMP2/CENXp FISH Probe
FG0059

Fluorescent in situ hybridization of formalin-fixed paraffin-embedded human colon cancer (FFPE) with LAMP2/CENXp FISH Probe. (Cat # FG0059).

LAMP2 (Texas Red)
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References

Matthew A. Gray, et. al. (2016). Cell Current Biology. DOI: 10.1016/j.cub.2016.05.070 Xinran Li, et. al. (2016) Nature Cell Biology, DOI: 10.1038/ncb3324 Maria Giovanna De Leo, et. al. (2016) Nature Cell Biology. DOI: 10.1038/ncb3386

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Exosome Biomarkers

New Discoveries on Exosome Related Research Dendritic cell-derived exosomes (Dex), with surface expression of MHC-peptide complexes, are able to interact with immune cells. Having conducted in advanced malignancies, these nanometer-sized Dexs are able to mediate T and NK cell-based immune response in patients as a feasible and safe immunotherapy for cancer. (The Journal of Clinical Investigation,2016) Tumor derived exosomes (TDEs) carry epithelial mesenchymal transition inducers to invade organ-specific cells and induce organotropic metastasis through stromal remodeling and pre-metastatic niche formation. Pharmacological agents targeting TDE biogenesis, secretion and function, such as heparanase/ syndecan-1 axis, may exert anti-metastatic activity. (Trends in Pharmacological Sciences,2016) Exosome-transmitted IncARSR, by acting as a competing endogenous RNA, can induce sunitinib resistance in renal cancer. IncARSR competitively binds miR-34/miR-449 to facilitate AXL and c-MET expression in renal cell carcinoma and promote sunitinib resistance. Thus, IncARSR may be a potential therapeutic target to restore drug sensitivity. (Cancer Cell,2016) Tumor-derived Exosomes in Tumor Microenvironment (Click to see your products of interest) Eight Product Categories and 770+ Products 314 Monoclonal Antibodies 209 Polyclonal Antibodies 54 Antibody Pairs 76 Recombinant Proteins 43 ELISA and Assay Kits 38 RNAi 6 FISH Probes 31 Cell Transient Overexpression Lysates Featured Products BIRC5 monoclonal antibody (M01), clone 5B10 H00000332-M01 Immunofluorescence staining of HeLa cells with BIRC5 monoclonal antibody (M01), clone 5B10 at the concentration of 10 ug/mL. HSP90AB1 monoclonal antibody, clone 5G4 MAB10686 Immunofluorescence staining of HeLa cells using HSP90AB1 monoclonal antibody, clone 5G4 (green), DRAQ5 fluorescent DNA dye (blue) and Alexa Fluor-555 phalloidin (red). TSG101 monoclonal antibody (M01), clone 5B7 H00007251-M01 Immunohistochemsitry analysis of formalin-fixed paraffin-embedded human kidney tissue using TSG101 monoclonal antibody, clone 5B7 at the concentration of 3 ug/mL. References Pitt, JM., et.al. (2016). The Journal of Clinical Investigation. DOI:10.1172/JCI81137 Syn, N., et.al. (2016). Trends in Pharmacological Sciences. DOI:10.1016/j.tips.2016.04.006 Qu, L., et. al. (2016). Cancer Cell. DOI:10.1016/j.ccell.2016.03.004 New Products   300 High standard Rabbit Polyclonal Antibodies for Immunohistochemsitry Analysis

Eukaryotic Transcription Cycle

New Discoveries on Eukaryotic Transcription Cycle Enhancers were found to be at the heart of deciphering contemporary regulatory biology. The discovery of enhancer RNA (eRNA)-producing transcription units as most functional enhancers has profound implications in future understanding of gene regulation, development and disease. (Nature Reviews Genetics, 2016) A pioneer factor FoxA was found to displace linker histone H1, thereby keeping enhancer nucleosomes accessible in chromatin and allowing other liver-specific transcription factors to bind and stimulate transcription. This discovery provided new evidence for nucleosomal configuration of open chromatin and the basis for its regulation mechanism. (Molecular Cell, 2016) A pooling-based approach was introduced to mapping quantitative trait loci (QTLs) for molecular-level traits. These QTLs not only affect local chromatin and transcription but also influence long-range chromosomal contacts, demonstrating a role for natural genetic variation in chromosomal architecture. The findings of this research suggested that transcription factor (TF) binding variation may play a crucial role in human phenotypic variation. (Cell, 2016) RNA polymerases  Name  Subcellular Location  Transcription Product(s)  RNA Polymerase I  Nucleolus  rRNAs  RNA Polymerase II  Nucleus  mRNAs, snRNAs, siRNAs, miRNAs  RNA Polymerase III  Nucleus  tRNAs, 5s rRNAs, snRNA U6, SRP RNA, other short RNAs  Abbreviation   Full Name   CPSF   Cleavage and polyadenylation specificity factor   CSTF   Cleavage stimulation factor   DSIF   DRB sensitivity-inducing factor complex   NELF   Negative elongation factor   PAFc   Polymerase-associated factor complex   PAB   Poly(A) binding protein   PAP   Poly(A) polymerase   SECs   Super elongation complexes   TF   Transcription factor Eight Product Categories and 10,000+ Products 3510 Monoclonal Antibodies 3562 Polyclonal Antibodies 505 Antibody Pairs 1958 Recombinant Proteins 127 ELISA and Assay Kits 1959 RNAi 164 FISH Probes 838 Cell Transient Overexpression Lysates Featured Products POLR2F monoclonal antibody (M02), clone 2G2 H00005435-M02 Immunofluorescence staining of HeLa cells with POLR2F monoclonal antibody (M02), clone 2G2 (Cat # H00005435-M02) at 10 ug/mL. EAF1 purified MaxPab mouse polyclonal antibody (B01P) H00085403-B01P Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) staining of human stomach (FFPE) with EAF1 purified MaxPab mouse polyclonal antibody (B01P) (Cat # H00085403-B01P) at 3 ug/mL. MLL/CEN11p FISH Probe FG0016 Fluorescent in situ hybridization of human lung adenosquamous cell carcinoma (FFPE) with MLL/CEN11p FISH Probe (Cat # FG0016). MLL (Texas Red) CEN11p (FITC) References Wenbo Li, et.al. (2016). Nature Review Genetics. DOI: 10.1038/nrg.2016.4 Makiko Iwafuchi-Doi, et. al. (2016) Molecular Cell. DOI: 10.1016/j.molcel.2016.03.001 Ashley K. Tehranchi, et. al. (2016) Cell. DOI: 10.1016/j.cell.2016.03.041 Related Products   300 New monoclonal antibodies for flow cytometry to accelerate your work with precision and accuracy