Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intracellular signals that mediate skeletal muscle protein loss and functional deficits due to muscular disuse are just beginning to be elucidated. Previously we showed that the activity of an NF-kappaB-dependent reporter gene was markedly increased in unloaded muscles, and p50 and Bcl-3 proteins were implicated in this induction. In the present study, mice with a knockout of the p105/p50 (Nfkb1) gene are shown to be resistant to the decrease in soleus fiber cross-sectional area that results from 10 days of hindlimb unloading. Furthermore, the marked unloading-induced activation of the NF-kappaB reporter gene in soleus muscles from WT mice was completely abolished in soleus muscles from Nfkb1 knockout mice. Knockout of the B cell lymphoma 3 (Bcl3) gene also showed an inhibition of fiber atrophy and an abolition of NF-kappaB reporter activity. With unloading, fast fibers from WT mice atrophied to a greater extent than slow fibers. Resistance to atrophy in both strains of knockout mice was demonstrated clearly in fast fibers, while slow fibers from only the Bcl3(-/-) mice showed atrophy inhibition. The slow-to-fast shift in myosin isoform expression due to unloading was also abolished in both Nfkb1 and Bcl3 knockout mice. Like the soleus muscles, plantaris muscles from Nfkb1(-/-) and Bcl3(-/-) mice also showed inhibition of atrophy with unloading. Thus both the Nfkb1 and the Bcl3 genes are necessary for unloading-induced atrophy and the associated phenotype transition.
 ...
PMID:Disruption of either the Nfkb1 or the Bcl3 gene inhibits skeletal muscle atrophy. 1554 1

HGAL, a prognostic biomarker in patients with diffuse large B-cell lymphoma and classic Hodgkin lymphoma, inhibits lymphocyte and lymphoma cell motility by activating the RhoA signaling cascade and interacting with actin and myosin proteins. Although HGAL expression is limited to germinal center (GC) lymphocytes and GC-derived lymphomas, little is known about its regulation. miR-155 is implicated in control of GC reaction and lymphomagenesis. We demonstrate that miR-155 directly down-regulates HGAL expression by binding to its 3'-untranslated region, leading to decreased RhoA activation and increased spontaneous and chemoattractant-induced lymphoma cell motility. The effects of miR-155 on RhoA activation and cell motility can be rescued by transfection of HGAL lacking the miR-155 binding site. This inhibitory effect of miR-155 suggests that it may have a key role in the loss of HGAL expression on differentiation of human GC B cells to plasma cell. Furthermore, this effect may contribute to lymphoma cell dissemination and aggressiveness, characteristic of activated B cell-like diffuse large B-cell lymphoma typically expressing high levels of miR-155 and lacking HGAL expression.
 ...
PMID:miR-155 regulates HGAL expression and increases lymphoma cell motility. 2209 45

GDC-0152 is a new type of chemical compound which can downregulate inhibitor of apoptosis protein. We previously reported that GDC-0152 induced apoptosis in HL-60 cells in a caspase-dependent manner. In this study, we have focused on GDC-0152-induced autophagy and the relationship between apoptosis and autophagy. We found that GDC-0152 can evoke autophagy flux as confirmed by the upregulation of LC3 and downregulation of p62. The conversion of LC3I to LC3II verified the existence of autophagy flux further. GDC-0152 induced autophagy through downregulating B cell lymphoma 2 and Bcl-2-interacting myosin-like coiled-coil protein, and upregulating WD-repeat domain phosphoinositide-interacting protein 1. Pretreating HL-60 cells with autophagy inhibitor Bafolimycin A1 reduced GDC-0152-induced apoptosis. However, pretreatment with caspase inhibitor Z-VAD-FMK had no effect on autophagy. Reactive oxygen species were released in GDC-0152-treated HL-60 cells but did not take part in the regulation of autophagy and apoptosis. In conclusion, our findings suggest that GDC-0152-induced autophagy can trigger apoptosis in HL-60 cells.
 ...
PMID:GDC-0152-induced autophagy promotes apoptosis in HL-60 cells. 2929 47

It is well known that autophagy serves a crucial role in renal tubular epithelial cell (RTEC) injury in the pathogenesis of chronic kidney disease (CKD). The accumulation of advanced oxidation protein products (AOPPs) also participates in the progression of CKD. However, the effects of AOPPs on autophagy remain unknown. To clarify the underlying mechanism of RTEC injury in CKD, the effect of AOPPs on HK-2 cells, an RTEC cell line, was investigated. The results of the present study revealed that AOPP exposure downregulated the expression of B-cell lymphoma-2-interacting myosin-like coiled-coil protein 1, reduced the conversion of microtubule-associated proteins 1 light chain 3B (LC3)-I to LC3-II and the formation of autophagosomes, and lead to an accumulation of p62. These results suggest that AOPPs may inhibit the autophagic activity of HK-2 cells. Furthermore, the aforementioned changes were mediated by the AOPP-phosphorylated phosphoinositide 3-kinase3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway; this was verified by treatment with LY294002, a PI3K inhibitor, which reversed the AOPP-induced changes. The present study also demonstrated that the activation of autophagy with rapamycin led to an improvement in the AOPP-induced overexpression of kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin, two biomarkers of RTEC injury, whereas inhibiting autophagy with chloroquine further increased their expression during AOPP treatment. Collectively, these results indicate that AOPPs may inhibit autophagy in RTECs via activation of the PI3K/AKT/mTOR pathway and that autophagy inhibition serves a role in AOPP-induced RTEC injury.
 ...
PMID:Advanced oxidation protein products inhibit the autophagy of renal tubular epithelial cells. 2955 65

Mutations in actins have been linked to several developmental diseases. Their occurrence across different cancers has, however, not been investigated. Using the cBioPortal database we show that human actins are infrequently mutated in patient samples of various cancers types. Nevertheless, ranking these studies by mutational frequency suggest that some have a higher percentage of patients with ACTB and ACTG1 mutations. Within studies on hematological cancers, mutations in ACTB and ACTG1 are associated with lymphoid cancers since none have currently been reported in myeloid cancers. Within the different types of lymphoid cancers ACTB mutations are most frequent in diffuse large B-cell lymphoma (DLBCL) and ACTG1 mutations in multiple myeloma. We mapped the ACTB and ACTG1 mutations found in these two cancer types on the 3D-structure of actin showing they are in regions important for actin polymer formation or binding to myosin. The potential effects of the mutations on actin properties imply that mutations in cytoplasmic actins deserve dedicated research in DLBCL and multiple myeloma.
 ...
PMID:Prevalence of Cytoplasmic Actin Mutations in Diffuse Large B-Cell Lymphoma and Multiple Myeloma: A Functional Assessment Based on Actin Three-Dimensional Structures. 3234 49