Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukemia associated inhibitor, LAI, reversibly inhibits DNA synthesis in normal human granulocyte-macrophage colony-forming units (CFU-GM). LAI is produced by myeloid leukemia cells, a subpopulation of normal nonadherent low-density mononuclear cells in peripheral blood and bone marrow, as well as by the human promyelocytic cell line HL-60. Normal low-density marrow cell absorbed LAI at 37 degrees C from HL-60 cell-conditioned medium. When normal marrow cells were treated with trypsin or chymotrypsin they lost their capacity to absorb LAI and also became insensitive to the inhibitory effect of LAI. These observations were taken as circumstantial evidence for the existence of a trypsin-sensitive LAI receptor on normal marrow cells, including CFU-GM. Glucocorticoid steroids (hydrocortisone, prednisolone, and dexamethasone) inhibited LAI production by acute myeloid leukemia (AML) cells, normal LAI-producing cells, and HL-60 cells. The fact that prostaglandin E1 (PGE) totally inhibited LAI production by normal cells and that indomethacin abrogated the inhibitory effect of adherent cells on LAI production suggested a role for adherent monocytic cells and PGE in the regulation of LAI production.
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PMID:Modulation of the production of leukemia associated inhibitor (LAI) and its interaction with granulocyte-macrophage colony-forming cells. 350 70

Leukemia-associated inhibitory activity suppresses colony and cluster formation in vitro cells derived from granulocyte-macrophage progenitor cells of normal donors. It does not inhibit these same progenitor cells from patients with leukemia and it may contribute to the proliferative advantage leukemia cells appear to possess over normal hematopoietic cells during acute leukemia. The inhibitory activity was isolated by a combination of procedures including: ultracentrifugation, Sephadex G-200, carboxymethylcellulose, SDS-polyacrylamide gel electrophoresis, thin-layer and preparative isoelectric focusing and concanavalin A-Sepharose. Leukemia-associated inhibitory activity was characterized as a glycoprotein. it was inactivated by trypsin, chymotrypsin, pronase and periodate treatment. It bound to and was eluted by alpha-methylmannose from concanavalin A-Sepharose columns and had an apparent Mr range of 450-550 000 and an isoelectric focus value between pH 4.6 and 4.9. Crude leukemia associated inhibitory activity was temperature sensitive but the more purified preparations were heat stable.
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PMID:Isolation and biochemical characterization of leukemia-associated inhibitory activity that suppresses colony and cluster formation of cells. 697 52

The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) are still to be investigated. Here, we studied the functional significance and the druggability of the oncogenic lncRNA MALAT1 in MM. Targeting MALAT1 by novel LNA-gapmeR antisense oligonucleotide antagonized MM cell proliferation and triggered apoptosis both in vitro and in vivo in a murine xenograft model of human MM. Of note, antagonism of MALAT1 downmodulated the two major transcriptional activators of proteasome subunit genes, namely NRF1 and NRF2, and resulted in reduced trypsin, chymotrypsin and caspase-like proteasome activities and in accumulation of polyubiquitinated proteins. NRF1 and NRF2 decrease upon MALAT1 targeting was due to transcriptional activation of their negative regulator KEAP1, and resulted in reduced expression of anti-oxidant genes and increased ROS levels. In turn, NRF1 promoted MALAT1 expression thus establishing a positive feedback loop. Our findings demonstrate a crucial role of MALAT1 in the regulation of the proteasome machinery, and provide proof-of-concept that its targeting is a novel powerful option for the treatment of MM.
Leukemia 2018 09
PMID:Drugging the lncRNA MALAT1 via LNA gapmeR ASO inhibits gene expression of proteasome subunits and triggers anti-multiple myeloma activity. 2948 87