PPM1B suppresses cervical carcinoma invasion by dephosphorylating MYPT1 at Thr853 and inactivating the PRMT5 epigenetic axis.

The spatiotemporal regulation of protein phosphorylation regulates cellular homeostasis, yet the phosphatase networks that actively dismantle oncogenic kinase signaling remain elusive. Here, we identify Mg2+-dependent protein phosphatase 1 (PPM1B) as a critical tumor suppressor in cervical carcinoma. Biochemically, PPM1B directly interacts with and dephosphorylates the myosin phosphatase (MP) regulatory subunit MYPT1 at its inhibitory Thr853 residue. We show that Rho-associated kinase (ROCK) activation by lysophosphatidic acid generates a high-affinity substrate profile, recruiting PPM1B to the Thr853-phosphorylated MYPT1. Crucially, this dephosphorylation drives the nuclear export of the MP holoenzyme, triggering a dual tumor-suppressive cascade. In the cytoplasm, reactivated MP dephosphorylates myosin light chain (MLC20) at Ser19 to prevent actomyosin-driven invasion. Concurrently, nuclear clearance of MYPT1 disrupts the PRMT5/histone H4 epigenetic axis, diminishing PRMT5 Thr80 phosphorylation and H4 symmetric dimethylation. Proteomic and phospho-kinase profiling indicates that PPM1B globally reprograms the malignant state, upregulating tumor suppressors (p53, Maspin) while attenuating epithelial-mesenchymal transition (EMT) drivers and survival networks (JNK, CREB). Finally, clinical biopsies of human squamous cell carcinoma demonstrate a strong correlation between reduced PPM1B expression and MYPT1 Thr853 hyperphosphorylation. Collectively, our findings establish PPM1B as a master catalytic switch that abrogates oncogenic signaling at both the cytoskeletal and epigenetic levels.