Matches in SemOpenAlex for { <https://semopenalex.org/work/W2049557712> ?p ?o ?g. }
- W2049557712 endingPage "1311" @default.
- W2049557712 startingPage "1297" @default.
- W2049557712 abstract "Abstract Nuclear receptors (NRs) are a superfamily of transcription factors whose genomic functions are known to be activated by lipophilic ligands, but little is known about how to deactivate them or how to turn on their nongenomic functions. One obvious mechanism is to alter the nuclear localization of the receptors. Here, we show that protein kinase C (PKC) phosphorylates a highly conserved serine (Ser) between the two zinc fingers of the DNA binding domain of orphan receptor hepatocyte nuclear factor 4α (HNF4α). This Ser (S78) is adjacent to several positively charged residues (Arg or Lys), which we show here are involved in nuclear localization of HNF4α and are conserved in nearly all other NRs, along with the Ser/threonine (Thr). A phosphomimetic mutant of HNF4α (S78D) reduced DNA binding, transactivation ability, and protein stability. It also impaired nuclear localization, an effect that was greatly enhanced in the MODY1 mutant Q268X. Treatment of the hepatocellular carcinoma cell line HepG2 with PKC activator phorbol 12-myristate 13-acetate also resulted in increased cytoplasmic localization of HNF4α as well as decreased endogenous HNF4α protein levels in a proteasome-dependent fashion. We also show that PKC phosphorylates the DNA binding domain of other NRs (retinoic acid receptor α, retinoid X receptor α, and thyroid hormone receptor β) and that phosphomimetic mutants of the same Ser/Thr result in cytoplasmic localization of retinoid X receptor α and peroxisome proliferator-activated receptor α. Thus, phosphorylation of this conserved Ser between the two zinc fingers may be a common mechanism for regulating the function of NRs." @default.
- W2049557712 created "2016-06-24" @default.
- W2049557712 creator A5016152202 @default.
- W2049557712 creator A5016465734 @default.
- W2049557712 creator A5021185476 @default.
- W2049557712 creator A5034516735 @default.
- W2049557712 creator A5036669790 @default.
- W2049557712 creator A5047924377 @default.
- W2049557712 creator A5058411506 @default.
- W2049557712 creator A5086029895 @default.
- W2049557712 creator A5086132910 @default.
- W2049557712 date "2007-06-01" @default.
- W2049557712 modified "2023-10-07" @default.
- W2049557712 title "Phosphorylation of a Conserved Serine in the Deoxyribonucleic Acid Binding Domain of Nuclear Receptors Alters Intracellular Localization" @default.
- W2049557712 cites W1503786870 @default.
- W2049557712 cites W1581213467 @default.
- W2049557712 cites W1967119334 @default.
- W2049557712 cites W1967658150 @default.
- W2049557712 cites W1969793909 @default.
- W2049557712 cites W1970991331 @default.
- W2049557712 cites W1971402402 @default.
- W2049557712 cites W1974184455 @default.
- W2049557712 cites W1974940941 @default.
- W2049557712 cites W1975717275 @default.
- W2049557712 cites W1979199349 @default.
- W2049557712 cites W1980508578 @default.
- W2049557712 cites W1982202242 @default.
- W2049557712 cites W1982350812 @default.
- W2049557712 cites W1983057459 @default.
- W2049557712 cites W1983541481 @default.
- W2049557712 cites W1984593949 @default.
- W2049557712 cites W1984638038 @default.
- W2049557712 cites W1985247182 @default.
- W2049557712 cites W1985827132 @default.
- W2049557712 cites W1985976602 @default.
- W2049557712 cites W1992475335 @default.
- W2049557712 cites W1993736467 @default.
- W2049557712 cites W1994242369 @default.
- W2049557712 cites W1994798295 @default.
- W2049557712 cites W2006227722 @default.
- W2049557712 cites W2008408111 @default.
- W2049557712 cites W2010583609 @default.
- W2049557712 cites W2016946690 @default.
- W2049557712 cites W201886038 @default.
- W2049557712 cites W2029033280 @default.
- W2049557712 cites W2035733956 @default.
- W2049557712 cites W2039307052 @default.
- W2049557712 cites W2047749014 @default.
- W2049557712 cites W2049408087 @default.
- W2049557712 cites W2050627047 @default.
- W2049557712 cites W2056128228 @default.
- W2049557712 cites W2057940509 @default.
- W2049557712 cites W2059415631 @default.
- W2049557712 cites W2064295256 @default.
- W2049557712 cites W2064544547 @default.
- W2049557712 cites W2064613822 @default.
- W2049557712 cites W2065283382 @default.
- W2049557712 cites W2066142272 @default.
- W2049557712 cites W2075385622 @default.
- W2049557712 cites W2075796826 @default.
- W2049557712 cites W2077604073 @default.
- W2049557712 cites W2079059309 @default.
- W2049557712 cites W2080080632 @default.
- W2049557712 cites W2080758856 @default.
- W2049557712 cites W2081532782 @default.
- W2049557712 cites W2081659044 @default.
- W2049557712 cites W2082205377 @default.
- W2049557712 cites W2091875431 @default.
- W2049557712 cites W2095872603 @default.
- W2049557712 cites W2096774529 @default.
- W2049557712 cites W2100435592 @default.
- W2049557712 cites W2104945250 @default.
- W2049557712 cites W2114555447 @default.
- W2049557712 cites W2117329869 @default.
- W2049557712 cites W2125182057 @default.
- W2049557712 cites W2148590099 @default.
- W2049557712 cites W2150093846 @default.
- W2049557712 cites W2155391261 @default.
- W2049557712 cites W2155458215 @default.
- W2049557712 cites W2156573432 @default.
- W2049557712 cites W2156831079 @default.
- W2049557712 cites W2164574768 @default.
- W2049557712 cites W2165427270 @default.
- W2049557712 cites W2168943199 @default.
- W2049557712 cites W2170645024 @default.
- W2049557712 cites W2170960648 @default.
- W2049557712 cites W2271149132 @default.
- W2049557712 cites W2349119987 @default.
- W2049557712 cites W2914278830 @default.
- W2049557712 cites W66239920 @default.
- W2049557712 cites W98247596 @default.
- W2049557712 doi "https://doi.org/10.1210/me.2006-0300" @default.
- W2049557712 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17389749" @default.
- W2049557712 hasPublicationYear "2007" @default.
- W2049557712 type Work @default.
- W2049557712 sameAs 2049557712 @default.
- W2049557712 citedByCount "82" @default.
- W2049557712 countsByYear W20495577122012 @default.