Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to conduct a semiquantitative immunohistochemical investigation into the levels of intermediary proteins within the nuclear factor (NF)-kappaB pathway throughout the menstrual cycle in a non-human primate, namely the baboon (Papio anubis), with and without endometriosis. Formalin-fixed eutopic (n = 2-4) and ectopic (n = 6-7) endometrial tissues from baboons at the mid-luteal phase were embedded in paraffin and examined for NF-kappaB pathway components (i.e. IkappaB kinase (IKK) alpha, IKKbeta, phosphorylated (phospho-) IkappaBalpha and phospho-NF-kappaB p65 subunit), ubiquitin, 19S proteasome and the NF-kappaB activator tumour necrosis factor (TNF)-alpha. Similarly, endometrial tissues from baboons at the late follicular, mid-luteal and menses phase (n = 2-4) were investigated to determine the levels of these proteins throughout the menstrual cycle. Cytoplasmic stromal IKKalpha and glandular 19S proteasome immunostaining was elevated in the ectopic endometrium, whereas levels of ubiquitin, phospho-p65, IKKbeta, TNF-alpha and nuclear 19S proteasome were similar in the eutopic and ectopic endometrium. A significant decrease in phospho-IkappaBalpha nuclear immunostaining was observed within glandular cells of the ectopic endometrium. In the eutopic endometrium, IKKalpha, ubiquitin and 19S proteasome immunostaining was elevated in different phases of the menstrual cycle, whereas levels of phospho-p65, IKKbeta, phospho-IkappaBalpha and TNF-alpha remained unchanged. We have demonstrated that, in the baboon endometriosis model, levels of IKKalpha immunostaining are elevated, whereas those of phospho-IkappaBalpha are reduced, consistent with the hypothesis that excessive NF-kappaB activity plays a role in reducing ectopic endometrial apoptosis, which contributes to the pathophysiology of endometriosis. Further studies are required to confirm a causal association between elevated IKKalpha levels and reduced endometrial apoptosis.
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PMID:Immunohistochemical study of the ubiquitin-nuclear factor-kB pathway in the endometrium of the baboon (Papio anubis) with and without endometriosis. 2079 50

Mantle cell lymphoma (MCL) is aggressive with poor prognosis. Due to t(11;14)(q13;q32), cyclin D1 is overexpressed. The in vitro activities of arsenic trioxide (As2O3) in MCL were investigated. In MCL lines Jeko-1 and Granta-519, As2O3 induced dose-dependent and time-dependent increases in apoptosis accompanied by cyclin D1 suppression. Downregulation of cyclin D1 resulted in decreased retinoblastoma protein phosphorylation, which led to repressed G1 progression to S/G2 phases. As2O3 did not affect cyclin D1 gene transcription. Instead, As2O3 activated glycogen synthase kinase-3beta (by tyrosine-216 phosphorylation) and IkappaB kinase alpha/beta (by serine-176/180 phosphorylation), both of which phosphorylated cyclin D1 at threonine-286, leading to its poly-ubiquitination and degradation in the proteasome. These observations were recapitulated partly in primary MCL samples obtained from patients refractory to conventional treatment. Our findings suggested that As2O3 might be clinically useful in MCL.
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PMID:Arsenic trioxide suppressed mantle cell lymphoma by downregulation of cyclin D1. 2394 14


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