4.3 Article

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

Journal

ONCOTARGET
Volume 8, Issue 31, Pages 51108-51122

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.17003

Keywords

p53; hnRNP L; apoptosis; IRES-mediated translation; post-transcriptional regulation

Funding

  1. Rural Development Administration, Republic of Korea [PJ01121602]
  2. BK21 Plus - Ministry of Education, Korea [10Z20130012243]
  3. POSCO (AP-TP, Green science)
  4. KT&G scholarship Foundation (KTG, Korea)

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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.

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