Antibody News

The tau protein is a microtubule associated protein found mostly in neuronal cells where it regulates the stability of axonal microtubules as well as kinesin-dependent transport. Tau is relevant in the study of various neurological disorders as abnormal post translational modifications can alter its structure and lead to protein aggregates. Tau is present on microtubules in neuronal cells and is also associated with the plasma membrane. Nuclear structures are also recognized by various tau antibodies indicating a potential nuclear function as well (1). Tau is alternatively spliced into six different isoforms that are expressed differentially during brain development (1). Tau interacts with microtubules through 3-4 microtubule binding domains, depending on the isoform, and this association can be regulated by various kinases and phosphatases (2). While tau phosphorylation is required for binding to and stabilizing microtubules,...

VPS34, vacuolar protein sorting 34, is the only identified Class III phosphoinositide-3 kinase (PI3K) in mammals and is ubiquitously expressed in all eukaryotic cells. VPS34 is a 100 kDa protein responsible for phosphorylating phosphatidylinositol to produce phosphatidylinositol 3-phosphate (PI3P). PI3P is an important intermediate in the development of the double-membraned autophagosome during autophagy, indicating a role for VPS34 in autophagy initiation. PI3P allows VPS34 to form complexes with ATG14L during the elongation of the autophagosome membrane. PI3P also acts as a scaffold for other proteins necessary for autophagy progression. ULK1 was recently identified as an activating kinase of the VPS34 complexes (1). ULK1 is activated by mTORC1 or AMPK during states of cell starvation. Active ULK1 phosphorylates Beclin-1, which is bound to ATG14L in the VPS34 complexes. This...

S6K is a serine/threonine kinase that is a member of the ribosomal S6 kinase (RSK) family. S6K exists in two main isoforms, S6K1 and S6K2, which can also be alternatively spliced to produce different splice forms. S6K1 has two major splicing products that are approximately 70 kDa and 85 kDa, known as p70S6K and p85S6K respectively. S6K is activated via phosphorylation by mTORC1 which relieves the autoinhibition of S6K. Active S6K phosphorylates the ribosomal S6 protein, which induces protein synthesis and cell growth and proliferation. S6K also phosphorylates EIF4B and EEF2K to upregulate protein synthesis. Many binding partners of S6K have been identified and indicate many roles for S6K in cellular growth, proliferation, and survival. S6K also plays a role in a negative feedback loop for mTOR signaling by phosphorylating RICTOR (1). RICTOR directly inhibits mTORC2 and AKT1 which ultimately impedes mTORC1 signaling.

Le et. al. used the...

Membrane fusion is an essential step during the trafficking of endosomes and vesicles throughout the cell. Membrane fusion events are facilitated by multisubunit tethering complexes (MTC) including CORVET and HOPS. These complexes interact with Rab GTPases and SNARE proteins to promote the fusion of endosomes and lysosomes (1). In yeast VPS41 is a component of the HOPS complex that is needed for transport of endosomes and Golgi-derived vesicles to the vacuole. The choice between these two substrates is facilitated by the phosphorylation of VPS1 by Yck3 (2). Carbrera et al. used VPS41 antibodies in western blots to examine phosphorylation status of VPS41 (2). Their study identified the importance of VPS41 phosphorylation in localization and in the regulation of either endosome or vesicle targeting (2). VPS41 also seems to play a role in the transport and fusion of autophagosomes. A group from the University of British Colombia...

C/EBP homologous protein (CHOP) is a transcription factor that regulates apoptosis in response to cellular stress. CHOP also known as growth arrest and DNA damage 153 (GADD153) was first cloned because of its induction in response to genotoxic stress such as UV irradiation. CHOP has now been shown to be induced mainly by ER-stress (1). CHOP is normally expressed at low levels and localizes to the cytoplasm. Cellular stress triggers an upregulation of CHOP levels and accumulation in the nucleus where it can act as either a transcriptional repressor or activator (1). CHOP contains an N-terminal transcriptional activation domain and a C-terminal basic leucine zipper domain responsible for DNA binding (1). In the nucleus CHOP forms heterodimers with C/EBP family transcription factors to either enhance promoter binding or to inhibit their activity. In this manner CHOP regulates genes involved in cell survival and death (1). ER-...

Cellular inhibitor of apoptosis protein-1 (cIAP-1) is an anti-apoptotic protein that is able to bind to caspases and inhibit their activity. Additionally cIAP-1 contains a RING domain with E3 ubiquitin ligase activity that is able to mediate the regulation of NF-kB signaling through the ubiquitination and degradation of various substrate proteins. Depending on cellular context, the RING domain of cIAP-1 can either promote or inhibit apoptosis. cIAP-1 functions in many cellular processes including inflammation, apoptosis, and the unfolded protein response making it an important player and potential target in various pathological conditions. For example, cIAP-1 levels were found to be a useful prognostic marker for the diagnosis and treatment of bladder cancer (1). Given the increased expression of cIAP-1 in cancer, small molecules targeting cIAP-1 for degradation have shown promise for sensitizing cancer cells to apoptosis (2). Depletion of IAP family proteins not only...

Autophagy is a process by which cells degrade and recycle damaged organelles or misfolded proteins. These various cargo are engulfed in a double-membrane structure called the autophagosome. The autophagosome then fuses with the lysosome to facilitate the degradation of the cargo. This process requires the concerted effort of an extensive network of proteins. One of the early steps of autophagosome assembly is the formation of the large multimeric ATG12-ATG5-ATG16 complex. This complex acts as an E3 ligase during the lipidation of ATG8. ATG8 is then incorporated into the expanding autophagosomal membrane and facilitates the recruitment of core autophagy machinery and substrates targeted for degradation. ATG16L2 is an isoform of ATG16 whose function is still unclear. While the isoform ATG16L1 is essential for autophagy, ATG16L2 does not seem to be important (1). In an examination of ATG16L2...

The heat-shock protein 90 (HSP90) family is a group of highly conserved molecular chaperones with important functions in protein folding and in signal transduction. The HSP90 protein structure is so well conserved that some HSP90 antibodies are reactive with a broad range of species from humans to chickens (1). In humans there are 17 known genes encoding the HSP90 family members. The HSP90 family consists of 4 different classes: HSP90AA, HSP90AB, HSP90B, and TRAP. These classes are defined by their diversity of functions and sub cellular localization. HSP90 isoforms are known to localize to the cytosol, nucleoplasm, endoplasmic reticulum, mitochondria, and chloroplasts. HSP90 is an abundant protein that maintains cellular homeostasis by promoting the proper folding of hundreds of substrate proteins referred to as clients. These clients range from protein kinases to transcription factors making HSP90 an essential component of many...

Fms-like tyrosine kinase-3 (FLT3) is a Type III receptor tyrosine kinase expressed by hematopoietic progenitor cells. FLT3 is also sometimes referred to as FLK2 or CD135. The FLT3 protein exists in two states- membrane bound (160 kDa) and cytoplasmic (140 kDa) (1). The FLT3 ligand induces autophosphorylation of FLT3 which allows binding of scaffold and effector molecules. Activated FLT3 is capable of phosphorylating and activating PI3K, PLC-γ, Shc, Grb2, and Src (2). FLT3 signaling ultimately activates the AKT and MAPK pathways to promote cell growth and survival. Mutations in FLT3 account for nearly one third of acute myeloid leukemia (AML) cases. The most common FLT3 derangement in AML is an internal tandem duplication (ITD) in the juxtamembrane domain. FLT3-ITD causes constituent activation of FLT3 signaling. Other activating mutations have also been identified, suggesting an important role for FLT3 in leukemogenesis. FLT3 overexpression correlates with a poor...

Akt1 is one of three isoforms of Akt belonging to the AGC family of serine/threonine kinases (Akt1, Akt2, and Akt3). All Akt isoforms contain an N-terminal Plekstrin Homology (PH) domain, a C-terminal regulatory domain, and a central catalytic kinase domain (1). Akt is a major downstream target of the PI3-K signaling pathway. The Akt1 isoform is fully activated by phosphorylation at three sites- T308, T450, and S473. Akt1 resides in an inactive state due to intramolecular interactions between the PH domain and the kinase domain. PI3-K signaling induces a conformational change that exposes the active sites to allow phosphorylation and activation of Akt1 (1). Akt plays a variety of roles in normal cellular metabolism, growth, proliferation, and survival. It has also been implicated in malignancies as a driver of angiogenesis, migration, and invasion. Recent studies have begun to tease apart the signaling specificity of the three Akt isoforms. Akt1 is expressed in many...

TSC2 is a tumor suppressor gene that encodes a 200 kDa protein called tuberin. TSC2 heterodimerizes with TSC1 to form a complex with GTPase-activating protein (GAP) activity. The C-terminus of TSC2 contains the GAP domain responsible for this catalytic activity. The complex was first discovered through its role in the tumor-forming condition Tuberous Sclerosis. Mutations in TSC1 and TSC2 can either destabilize the complex or compromise the GAP activity. The TSC1-TSC2 complex acts as a GAP for the small G-protein Rheb, expressed ubiquitously throughout the body (1). Rheb inhibits mTOR signaling to downregulate protein synthesis and cell growth. Thus in the absence of TSC1-TSC2, mTOR signaling allows unchecked cellular growth and proliferation. TSC1-TSC2 acts as a nutrient sensor for amino acids, growth factors, hormones, etc. and mediates cell cycle progression. The TSC1-TSC2 complex can be phosphorylated at a number of sites that are either activating or inactivating....

TSC1 is a tumor suppressor gene that encodes a 130 kDa protein called hamartin. TSC1 was first identified as an oncogenic driver of Tuberous Sclerosis, a condition characterized by numerous benign tumors of the skin, brain, heart, and lungs. A mutation in TSC1 is responsible for the uncontrolled growth characteristic of these tumors. This discovery led to a greater understanding of the physiologic role of TSC1 as a negative cell cycle regulator. The distinct but related gene TSC2 encodes a 200 kDa protein called tuberin. TSC1 and TSC2 heterodimerize to form a complex that acts as a GTPase-activating protein (GAP) for the G-protein Rheb (1). Rheb is a member of the Ras family that inhibits mTORC1 signaling when activated by the TSC1-TSC2 complex. mTORC1 signaling promotes cell growth and proliferation and aberrant signaling promotes tumor formation. The TSC1-TSC2 complex acts as a sensor for levels of growth factors, amino acids, and other...