Multiple Roles of Vestigial-Like Family Members in Tumor Development.

Noritaka Yamaguchi

doi:10.3389/fonc.2020.01266

Abstract

Vestigial-like family (VGLL) members are mammalian orthologs of vestigial gene in Drosophila, and they consist of four homologs (VGLL1–4). VGLL members have TDU motifs that are binding regions to TEA/ATSS-DNA-binding domain transcription factor (TEAD). Through TDU motifs, VGLL members act as transcriptional cofactors for TEAD. VGLL1-3 have single TDU motif, whereas VGLL4 has two tandem TDU motifs, suggesting that VGLL4 has distinct molecular functions among this family. Although molecular and physiological functions of VGLL members are still obscure, emerging evidence has shown that these members are involved in tumor development. Gene alterations and elevated expression of VGLL1-3 were observed in various types of tumors, and VGLL1-3 have been shown to possess tumorigenic functions. In contrast, down-regulation of VGLL4 was detected in various tumors, and the tumor-suppressing role of VGLL4 has been demonstrated. In this review, we summarize the recently identified multiple roles of VGLL members in tumor development and provide important and novel insights regarding tumorigenesis.

Highlights

Vestigial-like family (VGLL) is composed of four homologous members (VGLL1, 2, 3, and 4) in mammals [1, 2]
VGLL1 dysregulation was detected in various types of tumor; gene alterations in VGLL2 and VGLL3 were observed in sarcoma
VGLL2 shares a high homology with VGLL3, and both genes are expressed in the myogenic lineage [53]

Summary

Introduction

Vestigial-like family (VGLL) is composed of four homologous members (VGLL1, 2, 3, and 4) in mammals [1, 2]. VGLL genes are orthologs of vestigial (vg) which was primarily identified as a gene required for wing development in Drosophila [3, 4]. Vg binds to the product of scalloped (sd), which belongs to a conserved transcription factor family having a TEA/ATSS-DNA-binding domain (TEAD). It lacks DNA-binding domains and binds to DNA as a Vg-Sd protein complex. VGLL1 was the first isolated mammalian VGLL member with structural and functional similarity to Vg [6]. VGLL1 was originally named TONDU (TDU), and the motif in VGLL members required for association with TEAD is known as the TDU motif. VGLL1-3 have a single TDU motif, whereas VGLL4 has two separated TDU motifs (Figure 1A), suggesting that VGLL1-3 and VGLL4 have distinct molecular functions [1, 2]

Objectives

Conclusion