PPM1G Human
Description
mRNA Splicing and Spliceosome Assembly
PPM1G dephosphorylates pre-mRNA splicing factors (e.g., SRSF3), enabling proper spliceosome assembly. Knockdown disrupts small nuclear ribonucleoprotein (snRNP) biogenesis and reduces survival motor neuron (SMN) complex stability .
Cell Cycle Regulation
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Dephosphorylates p21/WAF1, promoting its proteasomal degradation and cell cycle progression .
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Modulates β-catenin degradation complex assembly, impacting Wnt signaling .
DNA Damage Response
PPM1G is recruited to DNA damage sites, where it dephosphorylates USP7S, stabilizing p53 and inducing cell cycle arrest .
Protein Translation
Dephosphorylates 4E-BP1, inhibiting cap-dependent translation. PI3K/AKT signaling inactivates PPM1G, enhancing translation in cancers .
Overexpression Correlates with Poor Prognosis
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TCGA-LIHC Data: PPM1G mRNA levels are 2.5-fold higher in HCC vs. normal tissues (p < 0.001) .
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Survival Analysis: High PPM1G expression reduces 5-year survival rates (HR = 1.8, p = 0.004) .
Functional Role in HCC Progression
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In Vitro: PPM1G knockdown reduces HepG2/Hep3B cell proliferation by 60% and invasion by 45% .
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In Vivo: Xenograft models show 70% smaller tumors with PPM1G silencing .
Transcriptional Activation
PPM1G is upregulated by MYC/MAX and coactivators (EP300, MED1) .
Post-Translational Modulation
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PI3K/AKT Pathway: Phosphorylates PPM1G at Ser⁴⁹⁵, inhibiting its phosphatase activity .
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Epigenetic Regulation: Promoter hypomethylation correlates with elevated expression in HCC .
Diagnostic Biomarker
PPM1G expression in serum exosomes shows 82% sensitivity and 75% specificity for early HCC detection .
Therapeutic Targeting
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Small-Molecule Inhibitors: Preclinical compounds reduce PPM1G activity by 90% in HCC cells .
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RNA Interference: siRNA-mediated knockdown synergizes with sorafenib in reducing tumor growth .
Interaction Network
PPM1G interacts with:
Product Specs
Product Science Overview
Protein Phosphatase 1G (PP1G), also known as Protein Phosphatase 2C gamma (PP2C-gamma), is a member of the PP2C family of serine/threonine protein phosphatases. These phosphatases are known to be negative regulators of cell stress response pathways. PP1G plays a crucial role in various cellular processes, including the regulation of the cell cycle, apoptosis, and transcription.
Recombinant human PP1G is typically prepared using bacterial expression systems, such as Escherichia coli (E. coli). The gene encoding PP1G is cloned into an expression vector, which is then introduced into the bacterial cells. The bacteria are cultured, and the expression of the recombinant protein is induced. After sufficient expression, the bacterial cells are lysed, and the recombinant protein is purified using chromatography techniques. The purified protein often includes a His-tag at the N-terminus to facilitate purification and detection .
PP1G is involved in the dephosphorylation of pre-mRNA splicing factors, which is essential for the formation of functional spliceosomes. This dephosphorylation activity is crucial for the regulation of various cellular processes. The enzyme catalyzes the removal of phosphate groups from serine and threonine residues in target proteins, thereby modulating their activity. The catalytic activity of PP1G is dependent on the presence of divalent metal ions, such as magnesium or manganese .
The activity of PP1G is tightly regulated by various mechanisms. One of the primary regulatory mechanisms involves the interaction with specific regulatory subunits that target PP1G to particular subcellular locations. These regulatory subunits often contain conserved binding motifs that facilitate their interaction with PP1G. Additionally, the activity of PP1G can be modulated by post-translational modifications, such as phosphorylation and acetylation. These modifications can alter the enzyme’s conformation and, consequently, its activity .
