Heterogeneous nuclear ribonucleoprotein (hnRNP) L promotes DNA damage-induced cell apoptosis by enhancing the translation of p53

Ji Young Seo, Do Yeon Kim, Seong Hoon Kim, Hyo Jin Kim, Hye Guk Ryu, Juhyun Lee, Kyung Ha Lee, Kyong Tai Kim

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The tumor suppressor p53 is an essential gene in the induction of cell cycle arrest, DNA repair, and apoptosis. p53 protein is induced under cellular stress, blocking cell cycle progression and inducing DNA repair. Under DNA damage conditions, it has been reported that post-transcriptional regulation of p53 mRNA contributes to the increase in p53 protein level. Here we demonstrate that heterogeneous nuclear ribonucleoprotein (hnRNP) L enhances p53 mRNA translation. We found that hnRNP L is increased and binds to the 5'UTR of p53 mRNA in response to DNA damage. Increased hnRNP L caused enhancement of p53 mRNA translation. Conversely, p53 protein levels were decreased following hnRNP L knock-down, rendering them resistant to apoptosis and arrest in the G2/M phase after DNA damage. Thus, our findings suggest that hnRNP L functions as a positive regulator of p53 translation and promotes cell cycle arrest and apoptosis.

Original languageEnglish
Pages (from-to)51108-51122
Number of pages15
JournalOncotarget
Volume8
Issue number31
DOIs
StatePublished - 7 Feb 2017

Keywords

  • Apoptosis
  • HnRNP L
  • IRES-mediated translation
  • Post-transcriptional regulation
  • p53

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