SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:DiVA.org:su-135980"
 

Search: onr:"swepub:oai:DiVA.org:su-135980" > Inhibition of RNA p...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Quin, JaclynStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Peter MacCallum Cancer Centre, Australia; University of Melbourne, Australia (author)

Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM/ATR signaling

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-07-06
  • Impact Journals, LLC,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:su-135980
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-135980URI
  • https://doi.org/10.18632/oncotarget.10452DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

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

Notes

  • RNA polymerase I (Pol I)-mediated transcription of the ribosomal RNA genes (rDNA) is confined to the nucleolus and is a rate-limiting step for cell growth and proliferation. Inhibition of Pol I by CX-5461 can selectively induce p53-mediated apoptosis of tumour cells in vivo. Currently, CX-5461 is in clinical trial for patients with advanced haematological malignancies (Peter Mac, Melbourne). Here we demonstrate that CX-5461 also induces p53-independent cell cycle checkpoints mediated by ATM/ATR signaling in the absence of DNA damage. Further, our data demonstrate that the combination of drugs targeting ATM/ATR signaling and CX-5461 leads to enhanced therapeutic benefit in treating p53-null tumours in vivo, which are normally refractory to each drug alone. Mechanistically, we show that CX-5461 induces an unusual chromatin structure in which transcriptionally competent relaxed rDNA repeats are devoid of transcribing Pol I leading to activation of ATM signaling within the nucleoli. Thus, we propose that acute inhibition of Pol transcription initiation by CX-5461 induces a novel nucleolar stress response that can be targeted to improve therapeutic efficacy.

Subject headings and genre

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

  • Chan, Keefe T. (author)
  • Devlin, Jennifer R. (author)
  • Cameron, Donald P. (author)
  • Diesch, Jeannine (author)
  • Cullinane, Carleen (author)
  • Ahern, Jessica (author)
  • Khot, Amit (author)
  • Hein, Nadine (author)
  • George, Amee J. (author)
  • Hannan, Katherine M. (author)
  • Poortinga, Gretchen (author)
  • Sheppard, Karen E. (author)
  • Khanna, Kum Kum (author)
  • Johnstone, Ricky W. (author)
  • Drygin, Denis (author)
  • McArthur, Grant A. (author)
  • Pearson, Richard B. (author)
  • Sanij, Elaine (author)
  • Hannan, Ross D. (author)
  • Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut (creator_code:org_t)

Related titles

  • In:Oncotarget: Impact Journals, LLC7:31, s. 49800-498181949-2553

Internet link

Find in a library

  • Oncotarget (Search for host publication in LIBRIS)

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