Antibody News

Integrins are a family of transmembrane proteins involved in diverse processes including cell adhesion, signal transduction, cell migration, and differentiation. They exist as heterodimers consisting of noncovalently linked alpha and beta subunits. Integrin complexes span the plasma membrane and link the cytoskeleton with the extracellular matrix. In mammals there are 18 alpha and 8 beta subunits that can assemble into 24 distinct integrin heterodimers with alternative splicing adding even more diversity. In addition to binding the extracellular matrix, integrins also bind to endogenous ligands including soluble proteins and cell surface proteins. Integrin alpha v beta 3 (Integrin αvβ3), also known as the vitronectin receptor, has important roles in angiogenesis and tumor metastasis and binds to a wide range of extracellular matrix proteins containing the RGD-motif. Integrin alpha v beta 3 is highly expressed in cells of the bone, placenta, and invasive tumors where it...

The transforming growth factor-β (TGF-beta) family consists of a wide variety of signaling proteins with roles in development. TGF-beta signaling controls growth, differentiation, and immune responses and is often misregulated in cancer. TGF-beta 1 is the most widely expressed and abundant isoform of the TGF-beta family. TGF-beta proteins signal through two classes of receptors: type I (TβRI) and type II (TβRI). These receptor proteins are serine threonine kinases found at the cell surface. Binding of TGF-beta induces the formation of a heterocomplex with TβRI and TβRII and leads to the phosphorylation of TβRI by TβRII. The active phosphorylated form of TβRI recruits and phosphorylates downstream effector SMAD proteins, which can then translocate to the nucleus where they can regulate transcription. Non-canonical signaling by TGF-beta 1 can also be mediated through various pathways including MAPKs, small GTPases, and PI3Ks. TGF-beta proteins are synthesized as pro-...

Noxa is a BH3-only protein involved in regulating cell death decisions. Noxa is a primary p53-response gene and is upregulated in response to p53 overexpression or DNA damage. Noxa can also be induced by alternative mechanisms including through a hypoxia-response element found in its promoter. Noxa localizes to mitochondria where it binds to Mcl1, an anti-apoptotic Bcl2 family member. Binding of Mcl1 by Noxa not only neutralizes its pro-survival effects but can also lead to proteasomal degradation of Mcl1 to further enhance apoptosis. While Noxa is important for induction of cell death in some cellular contexts, overexpression of Noxa does not always lead to a strong apoptotic response. This suggests Noxa-induced cell death may depend on the levels of other Bcl2-like and BH3-only proteins within the cell. While the relevance of Noxa in tumor suppression is unclear insight into the regulation of...

Autophagy is important for the removal of damaged organelles or proteins as well as for the regulation of cellular homeostasis in response to stress. Proteins or organelles that are targeted for degradation are engulfed in a double-membrane structure called the autophagosome that eventually fuses with the lysosome to mediate cargo degradation. Atg5 plays an important regulatory role in the early steps of this process. During early autophagosome assembly Atg5 is conjugated to Atg12, an ubiquitin-like protein, and associates with Atg16. This complex of Atg5-Atg12/Atg16 forms a large multimeric complex and localizes to early autophagsome structure where it plays an essential role in the lipidation of Atg8. Atg8 is another ubiquitin-like protein that, upon lipidation, inserts into the autophagosome membrane to help recruit additional lipid components and autophagy machinery as well as cargo targeted for degradation. The...

Scavenger receptors play important roles in homeostasis and innate immunity by binding to endogenous and foreign molecules. Scavenger receptors on the plasma membrane of macrophages bind to ligand and allow their internalization and can also mediate pro- or anti-inflammatory signaling. The plasma membrane glycoprotein CD163 is a member of the scavenger receptor cysteine-rich (SRCR) protein family. CD163 contains nine SRCR domains and is expressed in macrophages and monocytes where it plays a role in innate immunity and regulation of inflammation in response to ligand binding. CD163 binds specifically to hemoglobin (Hb)-haptoglobin (Hp) complexes produced during hemolysis to allow their internalization and lysosomal degradation. Additionally, CD163 has been shown to bind other ligands including some bacterial or viral pathogens. Recognition of these ligands leads to internalization and breakdown as well as...

During autophagy ubiquitinated cargo or substrates are engulfed in a double-membrane autophagosome and transported to the lysosome for degradation. This process is important for maintaining cellular homeostasis and for degrading damaged organelles or misfolded protein aggregates. p62, also known as sequestosome 1 (SQSTM1), is an autophagy receptor that recognizes and recruits cargo to the autophagosome through its interaction with Atg8. Atg8, known as LC3 in mammals, is a ubiquitin-like protein that is conjugated to the lipid phosphatidylethanolamine which anchors it into the double-membrane phagopore structure. Atg8/LC3 is essential for binding to and recruiting the core autophagy machinery through an Atg8 interacting motif (AIM) or through the LC3-Interacting region (LIR). AIM/LIR containing autophagy receptors, including p62/SQSTM1, recognize ubiquitinated proteins and target them to the autophagosome for destruction. Autophagy is...

Human leukocyte antigen G (HLA G) is a major histocompatibility complex (MHC) class I molecule that is primarily expressed in the placenta and is essential for the immune tolerance of the fetus during pregnancy. Unlike many HLA genes, HLA G has relatively few variants and is alternatively spliced into seven different isoforms. Of these isoforms four are membrane-bound while three are predicted to be soluble. Both the membrane-bound and soluble form of HLA G can induce immune tolerance by binding to inhibitory receptors on various immune cells including macrophages and monocytes. HLA G is aberrantly expressed in diseases such as multiple sclerosis, viral infection, and cancer. In cancer HLA G is thought to function as an important mechanism to escape the immune system. Elevated HLA G is found in cancer patient serum and may serve as an important diagnostic tool to distinguish between malignant and benign tumors as well as sensitivity to chemotherapeutic agents.
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Cluster of differentiation 74 (CD74) is an important integral membrane protein that serves as a chaperone for MHC class II molecules. CD74, also known as the invariant chain or Ii, is needed for the proper folding and trafficking of MHC class II in antigen presenting cells. CD74 serves as a scaffold for MHC class II assembly. During assembly CD74 blocks the peptide binding cleft of MHC class II to prevent binding of antigenic peptides. Following endocytosis of antigen the CD74-MHC class II complex is trafficked to the endosome where CD74 is digested leaving only the 9 amino acid CLIP peptide in the binding cleft. CLIP peptide can then be released to allow the binding of antigenic peptide and the trafficking of the antigen bound MHC molecules to the plasma membrane. CD74 also plays important roles in various cell signaling pathways including the activation of nuclear factor-kB during B-cell maturation. CD74's function in B-cell...

Integrins are a large family of trasmembrane proteins involved in cell adhesion and form a link between the intracellular cyskeletal proteins and extracellular matrix proteins. Integrins exist as heterodimers consisting of alpha and beta subunits. In addition to cell adhesion these integrin complexes play key roles in diverse processes such as signal transduction, cell migration, proliferation, differentiation, and apoptosis. Integrins consist of three domains: the extracellular domain, the transmembrane domain, and the cytoplasmic tail. The large globular extracellular domain is responsible for ligand binding while the transmembrane region is a single-pass α-helix. The cytoplasmic tails are short unstructured regions that form salt bridges between alpha and beta proteins as well as interact with adaptor proteins that link to the cytoskeleton. Integrin complexes are able to signal bidirectionally. Ligand binding on the outside of the cell can trigger an intracellular...

Heat-shock protein 90 (Hsp90) is a conserved ATP-dependent chaperone with diverse cellular functions. Hsp90 is ubiquitously expressed but is further induced upon cellular stress such as heat-shock or nutrient deprivation. Hsp90 is essential for the proper folding of a diverse set of proteins called clients. These client proteins consist of important signal transduction proteins including transcription factors, kinases, and steroid hormone receptors. By regulating the final folding steps of these client proteins Hsp90 plays an important role in many cellular signaling pathways. Hsp90 exists in two closely related isoforms; Hsp90A localizes to the cytosol while Hsp90B localizes to the endoplasmic reticulum. Hsp90A exists as a member of a protein complex and is associated with various co-chaperone proteins that mediate substrate recruitment. While the mechanism of protein folding is unclear an Hsp90A dimer is thought to bind to partially...

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor consisting of alpha and beta subunits. The levels of functional HIF-1 in the cell depends on the level of oxygen allowing cells to respond to hypoxic conditions. HIF-1α is a ubiquitously expressed protein containing an oxygen-dependent degradation domain that under normal conditions regulates its constant degradation. HIF-1 beta, on the other hand, is a stable constitutively expressed protein that localizes to the nucleus. Upon stabilization of HIF-1α by low oxygen it translocates to the nucleus where it dimerizes with HIF-1 beta to form an active transcription factor. HIF-1 recognizes and binds to hypoxia response elements (HRE) in the promoters of target genes including those involved in angiogenesis and cell proliferation such as vascular endothelial growth factor (VEGF) and ...

Microtubule-associated protein-1 light chain 3 (LC3/LC3B) is a ubiquitin-like protein involved in the formation of the autophagosome. It is homologous to the yeast Atg8 protein. Autophagosomes are important for the degradation and recycling of intracellular cargo such as misfolded proteins or damaged organelles. Upon induction of autophagy, LC3 is conjugated to the lipid phosphatidylethanolamine (PE) by the Atg12-Atg5-Atg16 protein complex. This lipidation is essential for the localization of LC3 to the assembling autophagosome where it recruits the core autophagy machinery. LC3 mediates membrane expansion in order to selectively engulf cargo and deliver it to the lysosome for degradation. Autophagy receptors, such as p62/SQSTM1, recognize specific ubiquitinated cargo. They also contain LC3-interacting regions (LIR) which allow them to deliver cargo to the...