SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:gup.ub.gu.se/119452"
 

Search: onr:"swepub:oai:gup.ub.gu.se/119452" > A natural transacti...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Collingwood, T N (author)

A natural transactivation mutation in the thyroid hormone beta receptor: impaired interaction with putative transcriptional mediators.

  • Article/chapterEnglish1997

Publisher, publication year, extent ...

  • 1997

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/119452
  • https://gup.ub.gu.se/publication/119452URI

Supplementary language notes

  • Language:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • The syndrome of resistance to thyroid hormone is characterized by elevated serum free thyroid hormones, failure to suppress pituitary thyrotropin secretion, and variable peripheral refractoriness to hormone action. Here we describe a novel leucine to valine mutation in codon 454 (L454V) of the thyroid hormone beta receptor (TR beta) in this disorder, resulting in a mutant receptor with unusual functional properties. Although the mutant protein binds ligand comparably to wild-type receptor and forms homo- and heterodimers on direct repeat, everted repeat, or palindromic thyroid response elements, its ability to activate transcription via these elements is markedly impaired. The hydrophobic leucine residue lies within an amphipathic alpha-helix at the carboxyl terminus of TR beta and the position of the homologous residue in the crystal structure of TR alpha indicates that its side chain is solvent-exposed and might interact with other proteins. We find that two putative transcriptional mediators (RIP140 and SRC-1) exhibit hormone-dependent association with wild-type TR. In comparison, the interaction of this natural mutant (L454V) and artificial mutants (L454A, E457A) with RIP140 and SRC-1 is markedly reduced. Furthermore, coexpression of SRC-1 is able to restore the transcriptional activity of the L454V mutant receptor, indicating that the interaction of this residue with accessory proteins is critical for transcriptional activation. Finally, the occurrence of the L454V mutation in resistance to thyroid hormone, together with impaired negative regulation of the thyroid-stimulating hormone alpha promoter by this mutant, suggests that the amphipathic alpha-helix also mediates hormone-dependent transcriptional inhibition, perhaps via interaction with these or other accessory factors.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Rajanayagam, O (author)
  • Adams, M (author)
  • Wagner, R (author)
  • Cavaillès, V (author)
  • Kalkhoven, E (author)
  • Matthews, C (author)
  • Nyström, Ernst,1941Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin,Institute of Internal Medicine(Swepub:gu)xnyser (author)
  • Stenlöf, Kaj,1965Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin,Institute of Internal Medicine(Swepub:gu)xstenk (author)
  • Lindstedt, G (author)
  • Tisell, L (author)
  • Fletterick, R J (author)
  • Parker, M G (author)
  • Chatterjee, V K (author)
  • Göteborgs universitetInstitutionen för invärtesmedicin (creator_code:org_t)

Related titles

  • In:Proceedings of the National Academy of Sciences of the United States of America94:1, s. 248-530027-8424

Internet link

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view