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279736 occurrences (No.90 in the rank) during 5 years in the PubMed. [no cache] 500 found

209) Using general and specific protein kinase inhibitors, we identified a protein kinase C (PKC) pathway that mediated TPA activation.

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PMID:24008983 DOI:10.1002/mc.22081

2015 Molecular carcinogenesis

* Differential 12-O-Tetradecanoylphorbol-13-acetate-induced activation of rat mammary carcinoma susceptibility Fbxo10 variant promoters via a PKC-AP1 pathway.

- Rat mammary carcinoma susceptibility 5a1 (Mcs5a1), which is concordant to human MCS5A1 breast cancer risk locus, mediates susceptibility by a non-mammary cell-autonomous mechanism associated with T cell differential expression of F-box protein 10 (Fbxo10). Human FBXO10, an evolutionarily conserved ubiquitin ligase gene, was shown to have a potential role in regulating cell death by controlling the degradation of Bcl-2, a key protein involved in apoptosis. Breast cancer susceptibility is controlled by interactions between environmental and genetic factors; therefore, we sought to determine if breast cancer risk-associated environmental chemicals interact with Mcs5a1 variants using luciferase reporter constructs containing 4.2 kb Fbxo10 promoters based on alleles of mammary cancer susceptible Wistar Furth (WF) and resistant Wistar Kyoto (WKY) rat strains. 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced activation of a 4.2 kb WF Fbxo10 promoter region, but lower levels of activation of the homologous WKY Fbxo10 promoter region. Using general and specific protein kinase inhibitors, we identified a protein kinase C (PKC) pathway that mediated TPA activation. We narrowed the possible PKCs to a member of the atypical PKC isoforms, namely PKCµ. We also determined that activator protein 1 (AP1) family member c-Fos mediated TPA activation of the 4.2 kb WF Fbxo10 promoter. TPA was shown to induce endogenous FBXO10 mRNA and FBXO10 protein in Jurkat cells, a human T cell line, with a maximal level of expression from 1.5 to 2.5 h after exposure. These results indicate that FBXO10/Fbxo10 expression is regulated by a PKC-dependent pathway acting through c-Fos, which binds AP1-specific DNA elements in Mcs5a1.

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(1)15 to	(19)4 types	(37)2 attention	(55)2 lineages
(2)9 sequence	(20)3 characteristics	(38)2 barriers	(56)2 measures
(3)7 and	(21)3 features	(39)2 computational	(57)2 miRNAs
(4)7 cell	(22)3 job	(40)2 constitutive	(58)2 molecular
(5)7 variations	(23)3 target	(41)2 criteria	(59)2 neuronal
(6)6 cognitive	(24)3 tendon	(42)2 deficits	(60)2 or
(7)6 genes	(25)3 therapy	(43)2 differences	(61)2 parameters
(8)6 surface	(26)3 type	(44)2 divergence	(62)2 phytotoxicity
(9)5 antibodies	(27)3 variation	(45)2 effect	(63)2 polymerase
(10)5 for	(28)2 null	(46)2 elements	(64)2 primers
(11)5 phobias	(29)2 ECM	(47)2 ethnocultural	(65)2 protein
(12)4 brain	(30)2 IgG	(48)2 extracellular	(66)2 proteins
(13)4 effects	(31)2 PCR	(49)2 fault	(67)2 recommendations
(14)4 growth	(32)2 age-dependent	(50)2 function	(68)2 requirements
(15)4 incidence	(33)2 analysis	(51)2 genetic	(69)2 self-efficacy
(16)4 manner	(34)2 antigen	(52)2 genomic	(70)2 targeted
(17)4 motor	(35)2 antigens	(53)2 information	(71)2 tests
(18)4 needs	(36)2 approach	(54)2 inhibitors

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--- WordNet output for specific --- =>特有の, 特効薬, 明確な, 特定の, 種の, はっきりした Overview of noun specific The noun specific has 2 senses (no senses from tagged texts) 1. particular, specific -- (a fact about some part (as opposed to general); "he always reasons from the particular to the general") 2. specific -- (a medicine that has a mitigating effect on a specific disease; "quinine is a specific for malaria") Overview of adj specific The adj specific has 4 senses (first 2 from tagged texts) 1. (39) specific -- ((sometimes followed by `to') applying to or characterized by or distinguishing something particular or special or unique; "rules with specific application"; "demands specific to the job"; "a specific and detailed account of the accident") 2. (5) specific -- (stated explicitly or in detail; "needed a specific amount") 3. specific -- (relating to or distinguishing or constituting a taxonomic species; "specific characters") 4. specific -- (being or affecting a disease produced by a particular microorganism or condition; used also of stains or dyes used in making microscope slides; "quinine is highly specific for malaria"; "a specific remedy"; "a specific stain is one having a specific affinity for particular structural elements") --- WordNet end ---