FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3137559999> ?p ?o ?g. }

• W3137559999 endingPage "361" @default.
• W3137559999 startingPage "343" @default.
• W3137559999 abstract "Background BIR repeat-containing ubiquitin conjugating enzyme (BRUCE) is a liver tumor suppressor, which is downregulated in a large number of patients with liver diseases. BRUCE facilitates DNA damage repair to protect the mouse liver against the hepatocarcinogen diethylnitrosamine (DEN)-dependent acute liver injury and carcinogenesis. While there exists an established pathologic connection between fibrosis and hepatocellular carcinoma (HCC), DEN exposure alone does not induce robust hepatic fibrosis. Further studies are warranted to identify new suppressive mechanisms contributing to DEN-induced fibrosis and HCC. Aim To investigate the suppressive mechanisms of BRUCE in hepatic fibrosis and HCC development. Methods Male C57/BL6/J control mice [loxp/Loxp; albumin-cre (Alb-cre)-] and BRUCE Alb-Cre KO mice (loxp/Loxp; Alb-Cre+) were injected with a single dose of DEN at postnatal day 15 and sacrificed at different time points to examine liver disease progression. Results By using a liver-specific BRUCE knockout (LKO) mouse model, we found that BRUCE deficiency, in conjunction with DEN exposure, induced hepatic fibrosis in both premalignant as well as malignant stages, thus recapitulating the chronic fibrosis background often observed in HCC patients. Activated in fibrosis and HCC, β-catenin activity depends on its stabilization and subsequent translocation to the nucleus. Interestingly, we observed that livers from BRUCE KO mice demonstrated an increased nuclear accumulation and elevated activity of β-catenin in the three stages of carcinogenesis: Pre-malignancy, tumor initiation, and HCC. This suggests that BRUCE negatively regulates β-catenin activity during liver disease progression. β-catenin can be activated by phosphorylation by protein kinases, such as protein kinase A (PKA), which phosphorylates it at Ser-675 (pSer-675-β-catenin). Mechanistically, BRUCE and PKA were colocalized in the cytoplasm of hepatocytes where PKA activity is maintained at the basal level. However, in BRUCE deficient mouse livers or a human liver cancer cell line, both PKA activity and pSer-675-β-catenin levels were observed to be elevated. Conclusion Our data support a BRUCE-PKA-β-catenin signaling axis in the mouse liver. The BRUCE interaction with PKA in hepatocytes suppresses PKA-dependent phosphorylation and activation of β-catenin. This study implicates BRUCE as a novel negative regulator of both PKA and β-catenin in chronic liver disease progression. Furthermore, BRUCE-liver specific KO mice serve as a promising model for understanding hepatic fibrosis and HCC in patients with aberrant activation of PKA and β-catenin." @default.
• W3137559999 created "2021-03-29" @default.
• W3137559999 creator A5015391208 @default.
• W3137559999 creator A5021452379 @default.
• W3137559999 creator A5024826620 @default.
• W3137559999 creator A5049275234 @default.
• W3137559999 creator A5061829398 @default.
• W3137559999 creator A5067793731 @default.
• W3137559999 creator A5073693925 @default.
• W3137559999 creator A5075354948 @default.
• W3137559999 date "2021-03-27" @default.
• W3137559999 modified "2023-09-25" @default.
• W3137559999 title "Baculovirus repeat-containing ubiquitin conjugating enzyme regulation of β-catenin signaling in the progression of drug-induced hepatic fibrosis and carcinogenesis" @default.
• W3137559999 cites W1534515820 @default.
• W3137559999 cites W1873311709 @default.
• W3137559999 cites W1963227271 @default.
• W3137559999 cites W1972858529 @default.
• W3137559999 cites W1975912195 @default.
• W3137559999 cites W1983734516 @default.
• W3137559999 cites W1986048086 @default.
• W3137559999 cites W2000369852 @default.
• W3137559999 cites W2006660938 @default.
• W3137559999 cites W2010428875 @default.
• W3137559999 cites W2013993442 @default.
• W3137559999 cites W2020376495 @default.
• W3137559999 cites W2021630989 @default.
• W3137559999 cites W2025635942 @default.
• W3137559999 cites W2052564025 @default.
• W3137559999 cites W2062196743 @default.
• W3137559999 cites W2064488040 @default.
• W3137559999 cites W2073010239 @default.
• W3137559999 cites W2076846359 @default.
• W3137559999 cites W2080788671 @default.
• W3137559999 cites W2087271869 @default.
• W3137559999 cites W2088629624 @default.
• W3137559999 cites W2100086304 @default.
• W3137559999 cites W2113632923 @default.
• W3137559999 cites W2125183288 @default.
• W3137559999 cites W2135743049 @default.
• W3137559999 cites W2153561951 @default.
• W3137559999 cites W2154522560 @default.
• W3137559999 cites W2161997928 @default.
• W3137559999 cites W2199551899 @default.
• W3137559999 cites W2338162624 @default.
• W3137559999 cites W2411225414 @default.
• W3137559999 cites W2422294114 @default.
• W3137559999 cites W2587610309 @default.
• W3137559999 cites W2734161211 @default.
• W3137559999 cites W2763700772 @default.
• W3137559999 cites W2773051121 @default.
• W3137559999 cites W2784418525 @default.
• W3137559999 cites W2793907677 @default.
• W3137559999 cites W2807378628 @default.
• W3137559999 cites W2811009228 @default.
• W3137559999 cites W2896191013 @default.
• W3137559999 cites W2897557611 @default.
• W3137559999 cites W2898361474 @default.
• W3137559999 cites W2914225706 @default.
• W3137559999 cites W2914760747 @default.
• W3137559999 cites W2969802526 @default.
• W3137559999 cites W3003625021 @default.
• W3137559999 cites W3014599953 @default.
• W3137559999 cites W3024187932 @default.
• W3137559999 cites W3029610374 @default.
• W3137559999 doi "https://doi.org/10.4254/wjh.v13.i3.343" @default.
• W3137559999 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8006081" @default.
• W3137559999 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33815677" @default.
• W3137559999 hasPublicationYear "2021" @default.
• W3137559999 type Work @default.
• W3137559999 sameAs 3137559999 @default.
• W3137559999 citedByCount "1" @default.
• W3137559999 countsByYear W31375599992023 @default.
• W3137559999 crossrefType "journal-article" @default.
• W3137559999 hasAuthorship W3137559999A5015391208 @default.
• W3137559999 hasAuthorship W3137559999A5021452379 @default.
• W3137559999 hasAuthorship W3137559999A5024826620 @default.
• W3137559999 hasAuthorship W3137559999A5049275234 @default.
• W3137559999 hasAuthorship W3137559999A5061829398 @default.
• W3137559999 hasAuthorship W3137559999A5067793731 @default.
• W3137559999 hasAuthorship W3137559999A5073693925 @default.
• W3137559999 hasAuthorship W3137559999A5075354948 @default.
• W3137559999 hasBestOaLocation W31375599991 @default.
• W3137559999 hasConcept C102658986 @default.
• W3137559999 hasConcept C104317684 @default.
• W3137559999 hasConcept C121608353 @default.
• W3137559999 hasConcept C126322002 @default.
• W3137559999 hasConcept C137620995 @default.
• W3137559999 hasConcept C181199279 @default.
• W3137559999 hasConcept C25602115 @default.
• W3137559999 hasConcept C2780035454 @default.
• W3137559999 hasConcept C2780559512 @default.
• W3137559999 hasConcept C30145163 @default.
• W3137559999 hasConcept C502942594 @default.
• W3137559999 hasConcept C55493867 @default.
• W3137559999 hasConcept C555283112 @default.
• W3137559999 hasConcept C60644358 @default.
• W3137559999 hasConcept C62478195 @default.
• W3137559999 hasConcept C71924100 @default.

• next