• cause apoptosis
  • The goal of this study was to determine whether plasmid expressed Bcr-Abl could cause apoptosis of K562 cells when specifically directed to the nucleus via strong nuclear localization signals (NLSs). (pubmedcentralcanada.ca)
  • In the nucleus, Bcr-Abl may cause apoptosis due to nuclear Abl's ability to stabilize p73 and activate its pro-apoptotic functions. (pubmedcentralcanada.ca)
  • When the levels of these components are thrown off, they can either no longer inhibit apoptosis of the cancer cells, a role fulfilled by BCR/ABL, or they cause apoptosis to be induced, in the same vein as Bax and cytochrome C. These components are key in the mitochondria, and due to this, it has been supported that apoptosis uses the mitochondrial apoptosis pathway. (wikipedia.org)
  • signaling pathway
  • A biomolecular target (most commonly a protein or nucleic acid) is a key molecule involved in a particular metabolic or signaling pathway that is associated with a specific disease condition or pathology or to the infectivity or survival of a microbial pathogen. (wikipedia.org)
  • oncogene
  • In the cytoplasm Bcr-Abl acts as an oncogene by interacting with multiple signal transduction pathways that transmit anti-apoptotic and mitogenic signals[ 14 ]. (pubmedcentralcanada.ca)
  • The gag-onc fusion protein (also written as Gag-v-Onc, with "v" indicating that the Onc sequence resides in a viral genome) is a general term for a fusion protein formed from a group-specific antigen ('gag') gene and that of an oncogene ('onc'), a gene that plays a role in the development of a cancer. (wikipedia.org)
  • tumor
  • Mislocalization of tumor suppressors, oncogenes, or factors involved in apoptosis result in aberrant functioning of these proteins, leading to disease. (pubmedcentralcanada.ca)
  • Suppression of NF-κB activation by expression of the so-called superrepressor form of IκBα blocked BCR-ABL-dependent xenograft tumor formation ( 6 ). (aacrjournals.org)
  • There are many different cellular components involved in the cycle of apoptosis such as, BCR/ABL, Bcl-2, Bax protein, and cytochrome C. The tumor suppressor gene p53 is also important in the cell cycle regulation of K562 cells. (wikipedia.org)
  • It also stabilizes a number of proteins required for tumor growth, which is why Hsp90 inhibitors are investigated as anti-cancer drugs. (wikipedia.org)
  • chimeric
  • Chimeric or chimera usually designate hybrid proteins made of polypeptides having different functions or physico-chemical patterns. (wikipedia.org)
  • Di- or multimeric chimeric proteins can be manufactured through genetic engineering by fusion to the original proteins of peptide domains that induce artificial protein di- or multimerization (e.g., streptavidin or leucine zippers). (wikipedia.org)
  • The purpose of creating fusion proteins in drug development is to impart properties from each of the "parent" proteins to the resulting chimeric protein. (wikipedia.org)
  • Several chimeric protein drugs are currently available for medical use. (wikipedia.org)
  • Many chimeric protein drugs are monoclonal antibodies whose specificity for a target molecule was developed using mice and hence were initially "mouse" antibodies. (wikipedia.org)
  • isoform
  • It has also been shown to bind (in a different conformation from the VEGF binding) to the BCR-ABL fusion protein, specifically inhibiting the drug-resistant T315I mutant isoform. (wikipedia.org)
  • PHLPP1α, which was the first PHLPP isoform to be characterized, lacks the N-terminal portion of the protein, including the Ras association domain. (wikipedia.org)
  • Gleevec
  • Although Gleevec is currently the "gold standard" drug of choice for Bcr-Abl-positive CML[ 3 - 5 ], resistance to treatment with Gleevec occurs. (pubmedcentralcanada.ca)
  • Other mechanisms for resistance include Bcr-Abl amplification or overexpression, clonal evolution, a decrease in Gleevec bioavailability or cell exposure, and upregulation of drug efflux pumps[ 6 , 10 ]. (pubmedcentralcanada.ca)
  • They used Gleevec to stimulate Bcr-Abl to go to the nucleus (by unknown mechanism), followed by nuclear entrapment by leptomycin B (LMB), a general inhibitor of nuclear export. (pubmedcentralcanada.ca)
  • pathways
  • Akt1 is also able to induce protein synthesis pathways, and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy, and general tissue growth. (wikipedia.org)
  • sequence
  • Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed. (uniprot.org)
  • This typically involves removing the stop codon from a cDNA sequence coding for the first protein, then appending the cDNA sequence of the second protein in frame through ligation or overlap extension PCR. (wikipedia.org)
  • That DNA sequence will then be expressed by a cell as a single protein. (wikipedia.org)
  • The protein can be engineered to include the full sequence of both original proteins, or only a portion of either. (wikipedia.org)
  • Hsp90 is highly conserved and expressed in a variety of different organisms from bacteria to mammals - including the prokaryotic analogue HtpG (high-temperature protein G) with 40% sequence identity and 55% similarity to the human protein. (wikipedia.org)
  • Therapeutics
  • Recombinant fusion proteins are created artificially by recombinant DNA technology for use in biological research or therapeutics. (wikipedia.org)
  • In addition to small molecules, biopharmaceuticals and especially therapeutic antibodies are an increasingly important class of drugs and computational methods for improving the affinity, selectivity, and stability of these protein-based therapeutics have also been developed. (wikipedia.org)
  • isoforms
  • Most isoforms share a common C-terminal domain, which contains two zinc finger motifs that are required for hetero- or homo-dimerization, and for interactions with other proteins. (cancerindex.org)
  • induces
  • Unexpectedly, we find that senescence induction by BCR-ABL and CBFB-MYH11 occurs through a DDR-independent pathway, whereas RUNX1-ETO induces senescence in a DDR-dependent manner. (umassmed.edu)
  • decrease
  • This mechanism is thought to be more efficient, resulting in an approximately 80% to 95% decrease in the protein and mRNA expression. (wikipedia.org)
  • cellular
  • It deals with the structure and function of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules. (wikipedia.org)
  • As a specific case, a Gag-v-Onc fusion protein from the Rous sarcoma virus is useful in illustrating the dual role that the fusion protein plays in both the viral and host cellular life cycle. (wikipedia.org)
  • Heat shock proteins, as a class, are among the most highly expressed cellular proteins across all species. (wikipedia.org)
  • Cancer
  • In the case of the murine leukemia viruses, a species of viruses capable of causing cancer in murines (mice), the viral life cycle can also be responsible for oncogenesis through a Gag-v-Onc fusion protein called "Mo-MuLV(src)", which is a Gag-v-Src protein capable of inducing oncogenesis in living mice. (wikipedia.org)
  • nuclear
  • The paralogous Brr6 and Brl1 are conserved integral membrane proteins of the nuclear envelope (NE) with an unclear role in nuclear pore complex (NPC) biogenesis. (bioportfolio.com)
  • novel
  • Altering the subcellular localization of signal transducing proteins is a novel approach for therapeutic intervention. (pubmedcentralcanada.ca)
  • For partial gene fusions, the shuffling of different active sites and binding domains have potential to result in new proteins with novel functions. (wikipedia.org)
  • In addition, PHLPP dephosphorylates conventional and novel members of the protein kinase C family at their hydrophobic motifs, corresponding to Ser-660 in PKCβII. (wikipedia.org)
  • PHLPP1 and 2 also dephosphorylate the hydrophobic motifs of two classes of the protein kinase C (PKC) family: the conventional PKCs and the novel PKCs. (wikipedia.org)
  • downregulation
  • A 22-nucleotide fragment of a transfer RNA regulates translation by binding to the mRNA of a ribosomal protein and increasing its expression, and downregulation of the fragment in patient-derived live. (bioportfolio.com)
  • In culture they exhibit much less clumping than many other suspension lines, presumably due to the downregulation of surface adhesion molecules by bcr:abl. (wikipedia.org)
  • receptor
  • The conventional PKCs can be activated by calcium and diacylglycerol, two important mediators of G protein-coupled receptor signaling. (wikipedia.org)