Bombyx mori p38 MAPK Regulates Cell Cycle Progression and Silk Gland Endoreplication via Interaction with Cell Cycle Genes

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 of Bombyx 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 of Bmp38 MAPK induced cell cycle arrest at both G1/S and G2/M phases and suppressed cell proliferation, whereas Bmp38 MAPK knockdown alleviated G1/S arrest and enhanced proliferation. Mechanistically, Bmp38 MAPK increased BmCyclin B expression while reducing the expression of BmCyclin E, BmCDK2 and BmCDK1. Protein interaction assays further confirmed interactions between Bmp38 MAPK and BmCDK2, BmCyclin E and BmCyclin B. Notably, Bmp38 MAPK significantly inhibited DNA synthesis in silk gland cells, suggesting that Bmp38 MAPK contributes 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.