PPM1D Antibodies

Structure of PPM1D

The protein molecule of the PPM1D gene has a molecular weight of approximately 61.8 kDa. Its size remains relatively stable among different species, but there may be slight fluctuations due to minor differences in the amino acid sequence.

The protein encoded by the PPM1D gene consists of 605 amino acids and its tertiary structure presents a typical globular protein folding pattern. This protein has a highly conserved N-terminal phosphatase catalytic domain in its structure, which is the core region for its serine/threonine phosphatase activity and can specifically recognize and dephosphorylate substrate proteins such as p53 and p38 MAPK. The C-terminal region of the PPM1D protein contains a nuclear localization signal sequence and multiple phosphorylation sites. These structural elements jointly regulate its localization and activity within the cell nucleus. In addition, the PPM1D protein contains a characteristic manganese ion binding site, which maintains the correct conformation of the catalytic center through the coordination of two manganese ions and is crucial for the exertion of its enzymatic activity.

Fig. 1 Schematic illustration of the mechanism regulating PPM1D protein stability.¹

Key structural properties of PPM1D:

• Contains an N-terminal phosphatase catalytic domain
• The central active site contains two manganese ions
• The C-terminal region contains a nuclear localization signal
• The substrate recognition site specifically binds phosphorylated p53 and MAPK and other substrate proteins

Functions of PPM1D

The main function of the protein encoded by the PPM1D gene is to negatively regulate the cellular stress response and DNA damage repair pathways. However, it is also involved in various cellular processes, including cell cycle checkpoint regulation, inflammatory response, and stem cell maintenance.

The expression regulation curve of the PPM1D gene exhibits a stress-induced characteristic, which is different from the continuous expression pattern of housekeeping genes. This indicates its inducible expression characteristics in the DNA damage response and its functional role as a negative feedback regulator of the signaling pathway.

Applications of PPM1D and PPM1D Antibody in Literature

1. Stoyanov, Miroslav, et al. "PPM1D activity promotes cellular transformation by preventing senescence and cell death." Oncogene 43.42 (2024): 3081-3093. https://doi.org/10.1038/s41388-024-03149-3

The research has found that the truncation mutation of the PPM1D gene can inhibit cell aging induced by DNA damage, allowing cells to continuously proliferate under radiation or oncogene stress, leading to genomic instability and soft agar tumor formation, thus confirming its carcinogenic potential.

2. Akamandisa, Mwangala P., Rita Nahta, and Robert C. Castellino. "PPM1D/WIP1 in medulloblastoma." Oncoscience 3.7-8 (2016): 186. https://doi.org/10.18632/oncoscience.318

The PPM1D/WIP1 genes are frequently amplified or overexpressed in medulloblastomas. They promote metastasis by regulating CXCR4 and cooperate with the SHH pathway to promote cancer. Targeting WIP1 alone or in combination with inhibiting SHH/CXCR4 provides a new treatment strategy for recurrent/refractory medulloblastomas.

3. Khadka, Prasidda, et al. "PPM1D mutations are oncogenic drivers of de novo diffuse midline glioma formation." Nature communications 13.1 (2022): 604. https://doi.org/10.1038/s41467-022-28198-8

The study found that the truncation mutation of PPM1D was a clonal driver event in 11% of diffuse intrinsic pontine gliomas, promoting tumor formation by regulating the cell cycle and the p53 pathway. MDM2 inhibitors have therapeutic potential.

4. Miller, Peter G., et al. "PPM1D modulates hematopoietic cell fitness and response to DNA damage and is a therapeutic target in myeloid malignancy." Blood 142.24 (2023): 2079-2091. https://doi.org/10.1182/blood.2023020331

The study found that PPM1D regulates the competitive adaptation and self-renewal of hematopoietic stem cells. Its activation enhances chemotherapy resistance but is weaker than that of p53 deficiency. Inhibiting PPM1D can enhance the efficacy of various cancers and is well tolerated in adult mice, supporting its use as a therapeutic target.

5. Takahashi, Masaki, et al. "PPM1D is directly degraded by proteasomes in a ubiquitination-independent manner through its carboxyl-terminal region." Journal of Biomedical Science 32.1 (2025): 88. https://doi.org/10.1186/s12929-025-01185-z

The study found that PPM1D is directly degraded by the 20S proteasome through the 35 amino acids at the C-terminus, and this process does not require ubiquitination. Proteasome inhibitors lead to the accumulation of PPM1D, and the combination of PPM1D inhibitors can synergistically enhance the anti-tumor effect, providing a new strategy for treatment.

Creative Biolabs: PPM1D Antibodies for Research

Creative Biolabs specializes in the production of high-quality PPM1D antibodies for research and industrial applications. Our portfolio includes monoclonal and polyclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom PPM1D Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our PPM1D antibodies, custom preparations, or technical support, contact us at email.