SENP1 inhibits aerobic glycolysis in Aβ1-42-incubated astrocytes by promoting PUM2 deSUMOylation

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Jan. 10, 2025

Alzheimer's disease (AD), the most prevalent form of dementia in elderly, involves critical changes such as reduced aerobic glycolysis astrocytes and increased neuronal apoptosis, both which are significant disease's pathology. In our study, treated with amyloid β1-42 (Aβ1-42) to simulate AD conditions exhibited upregulated expressions small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1) Pumilio RNA Binding Family Member 2 (PUM2), alongside decreased levels Nuclear factor erythroid 2-related (NRF2). SENP1 is notably SUMOylation enzyme Aβ1-42-exposed astrocytes. Functional assays including Ni2+-Nitrilotriacetic acid (NTA) agarose bead pull-down co-immunoprecipitation (Co-IP) confirmed SENP1's role actively deSUMOylating PUM2, thereby enhancing its stability expression. The interaction between PUM2 3' untranslated region (3'UTR) NRF2 mRNA reduces levels, subsequently diminishing transcriptional activation glycolytic enzymes, Hexokinase (HK1) Glucose Transporter (GLUT1). These contribute observed reduction function astrocytes, exacerbating apoptosis. Targeted interventions, knockdown Senp1 or Pum2 overexpression APPswe/PSEN1dE9 (APP/PS1) transgenic mice, effectively HK1 GLUT1 alleviated cognitive impairment. findings highlight important roles SENP1/PUM2/NRF2 pathway influencing glucose metabolism presenting new potential therapeutic targets for AD. 1. deSUMOylates expression Aβ1-42-microenvironment. 2. binds reducing 3. Reduced promoting effects on 4. decreases leading an increase co-culture apoptosis

Language: Английский

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SENP1-mediated deSUMOylation of YBX1 promotes colorectal cancer development through the SENP1-YBX1-AKT signaling axis

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

Language: Английский

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The SUMO Family: Mechanisms and Implications in Thyroid Cancer Pathogenesis and Therapy

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2408 - 2408

Published: Oct. 21, 2024

(1) Background: Small ubiquitin-like modifiers (SUMOs) are pivotal in post-translational modifications, influencing various cellular processes, such as protein localization, stability, and genome integrity. (2) Methods: This review explores the SUMO family, including its isoforms catalytic cycle, highlighting their significance regulating key biological functions thyroid cancer. We discuss multifaceted roles of SUMOylation DNA repair mechanisms, modulation receptor activities, particularly context (3) Results: The aberrant machinery contributes to tumorigenesis through altered gene expression immune evasion mechanisms. Furthermore, we examine therapeutic potential targeting pathways cancer treatment, emphasizing need for further research develop effective inhibitors. (4) Conclusions: By understanding intricate biology, can pave way innovative strategies improve outcomes patients with advanced tumors.

Language: Английский

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Transcription factor PRRX1-activated ANXA6 facilitates EGFR-PKCα complex formation and enhances cisplatin sensitivity in bladder cancer

Life Sciences, Journal Year: 2024, Volume and Issue: 359, P. 123228 - 123228

Published: Nov. 9, 2024

Language: Английский

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ANXA6 expression as a potential indicator of tumor diagnosis, metastasis and immunity in nasopharyngeal carcinoma

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 283, P. 137809 - 137809

Published: Nov. 21, 2024

Language: Английский

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