ArticleThe Journal of biological chemistry2009
X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 157 citations in OpenAlex.
- USP13 Downregulation Distinguishes Malignant from Adjacent Non-Neoplastic Prostate Tissue and Suggests Altered PTEN-Related Regulatory Pathways in a Korean Cohort.Life (Basel, Switzerland) · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Tuning ubiquitin transfer by RING E3 ubiquitin ligases through the linchpin residue.Life science alliance · 2025Article
- Article
- SR-A3 suppresses AKT activation to protect against MAFLD by inhibiting XIAP-mediated PTEN degradation.Nature communications · 2025Article
- A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins.Cancers · 2025Review
- WWP1 targeting PTEN for polyubiquitination to promote bone metastasis of luminal breast cancer.Scientific reports · 2024Article
- Article
- A critical role of the endothelial S-phase kinase-associated protein 2/phosphatase and tensin homologue axis in angiogenesis and psoriasis.The British journal of dermatology · 2024Article
- The Correlations between the Intensity of Histopathological Ubiquitin-Specific Protease 11 Staining and Progression of Prostate Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Reciprocal negative feedback regulation of ATF6α and PTEN promotes prostate cancer progression.Cellular and molecular life sciences : CMLS · 2023Article
- Protein post-translational modifications in the regulation of cancer hallmarks.Cancer gene therapy · 2023Review
- TSPAN32 suppresses chronic myeloid leukemia pathogenesis and progression by stabilizing PTEN.Signal transduction and targeted therapy · 2023Article
- Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.Biomolecules · 2023Review
- The Role of PTEN in Epithelial-Mesenchymal Transition.Cancers · 2022Review
- Review
- Subcellular localization of X-linked inhibitor of apoptosis protein (XIAP) in cancer: Does that matter?BBA advances · 2022Review
- E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability.Cell death & disease · 2021Article
- Neddylation of PTEN regulates its nuclear import and promotes tumor development.Cell research · 2021Article
- The E3 Ubiquitin Ligase HOIP inhibits Cancer Cell Apoptosis via modulating PTEN stability.Journal of Cancer · 2021Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptotic cell death plays a normal role in various physiological processes, and deregulated apoptosis is a hallmark of several diseases, including cancer. Cell fate is dictated by the balance between pro- and antiapoptotic factors. Akt is one of these antiapoptotic factors, which must be activated through phosphorylation. The phosphorylation of Akt has previously been shown to be promoted by X-linked inhibitor of apoptosis protein (XIAP), another antiapoptotic protein dictating the fate of normal and cancer cells. However, the underlying mechanisms are poorly understood. We have observed that XIAP associates with PTEN (phosphatase and tensin homolog deleted on chromosome ten), the best characterized negative regulator of Akt phosphorylation, in vitro and in vivo. XIAP knockdown reduces constitutive mono- and polyubiquitination of PTEN, increases PTEN protein levels, and prevents nuclear accumulation of PTEN. Overexpression of XIAP induces polyubiquitination of PTEN and proteasome-dependent decrease of PTEN protein levels. RNA interference experiments showed that XIAP-induced regulation of Akt phosphorylation is PTEN-dependent. Additional experiments confirmed that XIAP also regulates PTEN in vivo; primary mouse embryonic fibroblasts derived from XIAP(-/-) mice contain higher levels of PTEN protein, less mono- and polyubiquitinated PTEN, and less nuclear PTEN than primary mouse embryonic fibroblasts derived from XIAP(+/+) mice. Finally, we found that XIAP can directly ubiquitinate PTEN in vitro. We thus propose that XIAP acts as an E3 ubiquitin ligase for PTEN and promotes Akt activity by regulating PTEN content and compartmentalization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.