How does PIAS1 regulate the cell migration process through SUMOylation?

1. What are the biological functions of SUMOylation?

SUMOylation is a dynamic and reversible post-translational modification process. Although its mechanism is similar to ubiquitination, its biological functions are significantly different. Unlike ubiquitination, which primarily mediates protein degradation, SUMOylation regulates protein subcellular localization, protein-protein interactions, and functional activity. This modification process involves three key enzymes: SUMO-activating enzyme (E1), SUMO-conjugating enzyme (E2), and substrate-specific SUMO ligase (E3).

Among various E3 ligases, the PIAS1 protein holds particular importance. It not only acts as a specific inhibitor of STAT1 signaling but also exhibits SUMO ligase activity, participating in the SUMOylation of multiple transcription factors and structural proteins. Studies have shown that PIAS1 plays a dual regulatory role in different types of tumors, promoting the proliferation and metastasis of certain tumor cells while inhibiting tumor progression dependent on specific signaling pathways. This complexity makes PIAS1 a critical target in cancer therapy research.

2. What is the application value of PIAS1 recombinant rabbit monoclonal antibody in related research?

The PIAS1 recombinant rabbit monoclonal antibody, as a research tool specifically recognizing the PIAS1 protein, holds significant value in SUMOylation mechanism studies and tumor biology research. This antibody is prepared by immunizing New Zealand White rabbits, exhibiting high affinity and specificity, enabling accurate detection of PIAS1 expression levels, subcellular localization, and interactions with substrate proteins.

In mechanistic studies, this antibody can be used for co-immunoprecipitation experiments to identify novel PIAS1 substrate proteins and their interaction networks. Through Western blot analysis, it can quantitatively detect changes in PIAS1 expression under various physiological and pathological conditions. Immunofluorescence techniques can reveal the spatial distribution characteristics of PIAS1 within cells, particularly its localization patterns in cytoskeletal structures.

In functional validation experiments, the PIAS1 recombinant rabbit monoclonal antibody can be used to assess the role of PIAS1 in cell migration and proliferation. By immunohistochemically detecting PIAS1 expression patterns in clinical samples, its correlation with tumor progression and prognosis can be explored. Additionally, this antibody can be used in drug screening platforms to evaluate the regulatory effects of candidate compounds on the PIAS1-SUMOylation signaling pathway.

3. How does SUMOylation proteomics identify novel PIAS1 substrates?

The study employed an integrated proteomics strategy, combining SUMO immunoprecipitation enrichment with stable isotope labeling technology, to systematically identify the SUMOylation network regulated by PIAS1. In the HeLa cell model, by comparing SUMOylation profiles under PIAS1 overexpression and knockout conditions, a total of 12,080 peptides from 544 SUMOylated proteins were quantified, with 91 modification sites on 62 proteins specifically regulated by PIAS1.

Functional enrichment analysis revealed that these PIAS1 substrate proteins participate in various biological processes, including transcriptional regulation, RNA binding, and cytoskeletal organization. Notably, several cytoskeleton-related proteins were identified as novel PIAS1 substrates, including β-actin, α-tubulin, and vimentin. Protein-protein interaction network analysis further confirmed the close association of these substrates in the dynamic regulation of the cytoskeleton.

4. How does VIM SUMOylation regulate cell migration?

The study found that PIAS1 specifically mediates SUMOylation of vimentin (VIM) at lysine residues 439 and 445. VIM, as a type III intermediate filament protein, is a key component of the cytoskeleton, involved in maintaining cell morphology and regulating cell movement. By constructing SUMOylation-deficient mutants (K439/445R), the study confirmed that this modification is crucial for VIM functional regulation.

Mechanistic studies showed that VIM SUMOylation significantly increases its solubility, promoting the formation of unit-length filaments and the dynamic reorganization of the intermediate filament network. In cell migration experiments, cells with SUMOylation-deficient VIM mutants exhibited markedly reduced migration ability, indicating that this modification plays a critical role in regulating cell movement. Further analysis revealed cross-regulation between SUMOylation and phosphorylation, collectively coordinating the dynamic remodeling of the cytoskeleton.

5. How does SUMOylation affect cytoskeletal dynamics?

The study elucidated the molecular mechanism by which PIAS1-mediated SUMOylation regulates cytoskeletal dynamics. Through reversible SUMOylation, PIAS1 stimulates the dephosphorylation of unit-length filaments, promoting their reintegration into the mature intermediate filament pathway. This dynamic regulatory mechanism directly affects the structural stability and functional plasticity of the cytoskeleton.

Fluorescence recovery after photobleaching experiments showed that SUMOylation significantly influences the dynamic distribution and turnover rate of VIM within cells. Compared to wild-type VIM, SUMOylation-deficient VIM mutants formed more stable filamentous structures, with reduced remodeling capacity of the intermediate filament network. These findings suggest that SUMOylation, as a fine-tuning mechanism, affects cell migration and motility by regulating the solubility and assembly dynamics of cytoskeletal proteins.

6. What are the clinical implications of this study?

This study provides new insights into understanding the mechanisms of tumor cell migration and invasion. PIAS1-mediated SUMOylation of cytoskeletal proteins may serve as a critical node in the regulation of tumor metastasis. Particularly in various epithelial-derived tumors, abnormalities in this modification mechanism may promote the invasive behavior of cancer cells.

From a therapeutic perspective, targeting the PIAS1-SUMOylation signaling pathway may offer new intervention strategies to inhibit tumor metastasis. By modulating the SUMOylation state of cytoskeletal proteins, it may be possible to influence the migratory and invasive potential of tumor cells. Additionally, PIAS1 expression levels and SUMOylation status may serve as potential biomarkers for tumor progression and prognosis.S

7. Which manufacturers provide PIAS1 recombinant rabbit monoclonal antibodies?Hangzhou Start Biotech Co., Ltd. has independently developed the "PIAS1 Recombinant Rabbit Monoclonal Antibody" (Product Name: PIAS1 Recombinant Rabbit mAb (S-1430-7), a high-specificity, high-sensitivity, and highly stable detection tool for SUMO E3 ligases. This product is developed using recombinant rabbit monoclonal antibody technology and has been rigorously validated across multiple platforms, including Western Blot (WB), Immunofluorescence (IF), and Immunoprecipitation (IP). It holds significant research value in SUMOylation regulation, transcription factor activity modulation, and tumor development.

Professional Technical Support: We provide comprehensive product technical documentation, including examples of nuclear localization changes under different cell stimulation conditions, co-localization/co-precipitation study recommendations with SUMOylated substrates or transcription factors, and specialized technical consultations, fully supporting breakthroughs in protein modification and gene regulation research.

Hangzhou Start Biotech Co., Ltd. is committed to providing high-quality, high-value biological reagents and solutions to global innovative pharmaceutical companies and research institutions. For more details about the "PIAS1 Recombinant Rabbit Monoclonal Antibody" or to request sample testing, please contact us.

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