Oncotarget

Research Papers:

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 and Kyong-Tai Kim _

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Oncotarget. 2017; 8:51108-51122. https://doi.org/10.18632/oncotarget.17003

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Abstract

Ji-Young Seo1, Do-Yeon Kim2,3, Seong-Hoon Kim2, Hyo-Jin Kim2, Hye Guk Ryu2, Juhyun Lee1, Kyung-Ha Lee2,4 and Kyong-Tai Kim1,2

1Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea

2Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea

3Department of Pharmacology, School of Dentistry, Kyungpook National University (KNU), Daegu, Gyeongbuk, Republic of Korea

4Division of Bio-technology and Convergence, Daegu Haany University (DHU), Gyeongsan-si, Gyeongbuk, Republic of Korea

Correspondence to:

Kyong-Tai Kim, email: ktk@postech.ac.kr

Keywords: p53, hnRNP L, apoptosis, IRES-mediated translation, post-transcriptional regulation

Received: September 06, 2016     Accepted: February 06, 2017     Published: April 10, 2017

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.


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