Open Access

ARTICLE

DNAJA4, DNAJB11 and DNAJC10 induce cell transformation by inhibiting p53 and oncogene-induced senescence

HYEON JU LEE¹, CHANG SEOP LEE¹, SI HOON KIM¹, SOOKYUNG KIM¹, JEONG MI KIM¹, SUN-WHA IM¹, YU-JIN JUNG², SEUNG-PYO HONG³, HYUNJUNG LEE³, JONG-IL KIM^3,4,5, JEONG A. HAN^1,*

1 Department of Biochemistry and Molecular Biology, Kangwon National University College of Medicine, Chuncheon, 24341, Republic of Korea
2 Department of Biological Sciences, Kangwon National University, Chuncheon, 24341, Republic of Korea
3 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 03080, Republic of Korea
4 Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
5 Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea

* Corresponding Author: JEONG A. HAN. Email:

BIOCELL 2024, 48(10), 1455-1464. https://doi.org/10.32604/biocell.2024.054538

Received 31 May 2024; Accepted 12 August 2024; Issue published 02 October 2024

Abstract

Objective: Transformation from normal cells to malignant cells is the basis for tumorigenesis. While this cell transformation is known to result from aberrant activation or inactivation of associated genes, these genes have not yet been fully identified. In addition, DNAJs, proteins with a J domain, are known to be molecular co-chaperones, but their cellular functions remain largely unexplored. In this context, we here identified DNAJA4, DNAJB11, and DNAJC10 as pro-transforming genes and elucidated their action mechanisms. Methods: Senescence-associated (SA)-β-galactosidase staining and western blotting were used to analyze cellular senescence and protein expression. Soft agar assay was used to analyze cell transformation. RNA sequencing data was downloaded from the Cancer Genome Atlas (TCGA) database. Results: We observed that overexpression of the three DNAJs inhibited oncogene-induced senescence (OIS) and the p53/p21^WAF1/CIP1 pathway under H-RAS^V12 expression in normal mouse embryonic fibroblasts (MEFs). Additionally, their overexpression inhibited p53-induced senescence. Moreover, overexpression of the three DNAJs induced neoplastic transformation in MEFs under H-RAS^V12 expression. Furthermore, RNA sequencing analysis showed that the three DNAJs are frequently overexpressed in cancer tissues compared to their matched normal tissues in various human cancers. Conclusion: These results suggest that the three DNAJs are pro-transforming genes whose aberrant overexpression contributes to cell transformation. These results also suggest that the three DNAJs induce cell transformation by inhibiting the senescence function of p53 and OIS. This study may contribute to understanding the molecular basis of cell transformation and the cellular functions of the three DNAJs.

---

Keywords

---