家蚕p38丝裂原活化蛋白激酶通过与细胞周期基因相互作用，调控细胞周期进程并促进丝腺体内复制

Abstract

The cell cycle is a fundamental biological process indispensable for life, and its orderly progression is governed by a complex signaling network. Although the p38 MAPK pathway plays important roles in regulating cell proliferation across metazoans, its mechanistic role in insect cell cycle progression remains poorly characterized, particularly in species with endoreplication systems. Here, we investigated the function and mechanism ofBombyx mori p38 MAPK(Bmp38 MAPK) in cell cycle regulation using the silkworm silk gland as a specialized endoreplication model. We found that the p38 MAPK is evolutionarily conserved from insects to mammals and exhibits both cytoplasmic and nuclear localization, with its expression peaking during the G1 phase. Overexpression ofBmp38 MAPKinduced cell cycle arrest at both G1/S and G2/M phases and suppressed cell proliferation, whereasBmp38 MAPKknockdown alleviated G1/S arrest and enhanced proliferation. Mechanistically,Bmp38 MAPKincreasedBmCyclin Bexpression while reducing the expression ofBmCyclin E,BmCDK2andBmCDK1. Protein interaction assays further confirmed interactions between Bmp38 MAPK and BmCDK2, BmCyclin E and BmCyclin B. Notably,Bmp38 MAPKsignificantly inhibited DNA synthesis in silk gland cells, suggesting thatBmp38 MAPKcontributes to the regulation of endoreplication. These findings reveal a possible role for p38 MAPK in insect cell cycle control and provide potential mechanistic insights into the regulation of endoreplication in the silkworm silk gland.