Topoisomerase II is regulated by translationally controlled tumor protein for cell survival during organ growth in Drosophila

Dae-Wook Yang,Robert Amson,Stephanie B Telerman,Jung-Wan Mok,Adam Telerman,Kwang-Wook Choi

doi:10.1038/s41419-021-04091-y

Abstract

Regulation of cell survival is critical for organ development. Translationally controlled tumor protein (TCTP) is a conserved protein family implicated in the control of cell survival during normal development and tumorigenesis. Previously, we have identified a human Topoisomerase II (TOP2) as a TCTP partner, but its role in vivo has been unknown. To determine the significance of this interaction, we examined their roles in developing Drosophila organs. Top2 RNAi in the wing disc leads to tissue reduction and caspase activation, indicating the essential role of Top2 for cell survival. Top2 RNAi in the eye disc also causes loss of eye and head tissues. Tctp RNAi enhances the phenotypes of Top2 RNAi. The depletion of Tctp reduces Top2 levels in the wing disc and vice versa. Wing size is reduced by Top2 overexpression, implying that proper regulation of Top2 level is important for normal organ development. The wing phenotype of Tctp RNAi is partially suppressed by Top2 overexpression. This study suggests that mutual regulation of Tctp and Top2 protein levels is critical for cell survival during organ development.

Highlights

Translationally controlled tumor protein (TCTP) is a growth control protein, initially found as P23 in murine and human tumor cells [1, 2]
The region between L4 and L5 in the posterior domain was significantly reduced with the near-complete loss of the posterior crossvein (PCV) (Fig. 1B’)
These results indicate that Top2 is required for normal growth and differentiation of the wing

Summary

Introduction

TCTP is a growth control protein, initially found as P23 in murine and human tumor cells [1, 2]. Conserved TCTP family proteins are involved in diverse biological processes, including growth, immune response, and cytoskeletal changes [3,4,5,6]. Abnormal regulation of TCTP has been implicated in the pathogenesis of growth-related diseases. Human TCTP is upregulated in various types of cancer cells or tissues [7,8,9]. Consistent with the anti-apoptotic function of TCTP, its overexpression can induce chemoresistance to cancer cells or tissues treated with anti-cancer drugs including etoposide [18,19,20,21,22]. Since the primary target of etoposide is Topoisomerase II (TOP2) [23,24,25], it is an intriguing question whether the antiapoptotic function of human TCTP is functionally related to TOP2

Methods

Results

Conclusion