JMY functions as actin nucleation-promoting factor and mediator for p53-mediated DNA damage in porcine oocytes.

Zili Lin,Suk Namgoong,Nam-Hyung Kim,Yong-Nan Xu,Qing-Yuan Sun

doi:10.1371/journal.pone.0109385

Abstract

Junction-mediating and regulatory protein(JMY) is a multifunctional protein with roles in the transcriptional co-activation of p53 and the regulation of actin nucleation promoting factors and, hence, cell migration; however, its role in the maturation of porcine oocytes is unclear. In the current study, we investigated functional roles of JMY in porcine oocytes. Porcine oocytes expressed JMY mRNA and protein, and the mRNA expression level decreased during oocyte maturation. Knockdown of JMY by RNA interference decreased the rate of polar body extrusion, validating its role in the asymmetric division of porcine oocytes. JMY knockdown also down-regulated the mRNA and protein levels of actin and Arp2/3. Furthermore, JMY accumulated in the nucleus in response to DNA damage, and JMY knockdown suppressed DNA damage-mediated p53 activation. In conclusion, our results show that JMY has important roles in oocyte maturation as a regulator of actin nucleation-promoting factors and an activator of p53 during DNA damage during DNA damages in porcine oocytes.

Highlights

In mammalian oocytes, dynamic actin polymerization and reorganization are essential for asymmetric spindle migration, polar body extrusion, and cytokinesis [1,2]
Upon processing of DNA double-strand breaks (DSBs), Junction-mediating and regulatory protein (JMY) forms a complex with strap and p300, which recruits PRMT5 into a coactivator complex that drives the p53 response [14,15] It is reported that DNA damage affects JMY activity, which is required for p53 transcriptional activity in MCF-7 cells [15]
JMY mRNA (Fig. 1B) and protein (Fig. 1C) were detected at GV, germinal vesicle breakdown (GVBD), and metaphase I (MI) stages; JMY expression was lowest at the MII stage

Summary

Introduction

Dynamic actin polymerization and reorganization are essential for asymmetric spindle migration, polar body extrusion, and cytokinesis [1,2]. Proteins which promote actin polymerization [3], such as formin 2 [4], spire [5], and the Arp2/3 complex [6,7] play essential roles in oocyte maturation. In addition with actin nucleators, nucleationpromoting factors (NPFs), which bind to and activate the Arp2/3 complex in response to Rho-GTPase signaling [3], are important for oocyte maturation. In addition to its role as an actin nucleation promoting factor, JMY was originally identified as a p53 coactivator, localizes to the nucleus during DNA damage [11,12,13]. Recent studies identify JMY as a target through which Mdm regulates p53 activity [12]

Methods

Results

Conclusion