ArticlePloS one2018
CHIP E3 ligase mediates proteasomal degradation of the proliferation regulatory protein ALDH1L1 during the transition of NIH3T3 fibroblasts from G0/G1 to S-phase.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Mitochondria-transliterated ALDH1L1 functions as a feedback regulator of redox homeostasis in cancer cells to enhance the resistance to pro-oxidative therapy.Cell death and differentiation · 2026Article
- Clinical implications of 10-formyltetrahydrofolate dehydrogenase expression in hormone receptor-positive breast cancer.Frontiers in oncology · 2026Article
- Effects of aging and anti-aging dietary restriction on regulators of the [NADPH]/[NADPFree radical biology & medicine · 2025Review
- Probing the metabolic regulator and candidate tumor suppressor ALDH1L1 as a target for non-small cell lung cancer gene therapy.Molecular therapy. Oncology · 2025Article
- Untargeted Metabolomics Reveals Dysregulation of Glycine- and Serine-Coupled Metabolic Pathways in an ALDH1L1-Dependent Manner In Vivo.Metabolites · 2024Article
- Regulatory mechanisms of one-carbon metabolism enzymes.The Journal of biological chemistry · 2023Review
- The roles of molecular chaperones in regulating cell metabolism.FEBS letters · 2023Review
- Abnormal downregulation of 10-formyltetrahydrofolate dehydrogenase promotes the progression of oral squamous cell carcinoma by activating PI3K/Akt/Rb pathway.Cancer medicine · 2023Article
- Exploratory Metabolomics Underscores the Folate Enzyme ALDH1L1 as a Regulator of Glycine and Methylation Reactions.Molecules (Basel, Switzerland) · 2022Article
- Genetic variants in ALDH1L1 and GLDC influence the serine-to-glycine ratio in Hispanic children.The American journal of clinical nutrition · 2022Article
- Transcription factor-based direct conversion of human fibroblasts to functional astrocytes.Stem cell reports · 2022Article
- Aldehyde Dehydrogenase 2 as a Therapeutic Target in Oxidative Stress-Related Diseases: Post-Translational Modifications Deserve More Attention.International journal of molecular sciences · 2022Review
- Structure of putative tumor suppressor ALDH1L1.Communications biology · 2022Article
- Profound changes in cerebrospinal fluid proteome and metabolic profile are associated with congenital hydrocephalus.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Article
- Sesquiterpene lactones ofChinese herbal medicines · 2021Review
- The Pup-Proteasome System Protects Mycobacteria from Antimicrobial Antifolates.Antimicrobial agents and chemotherapy · 2021Article
- Aldh1l2 knockout mouse metabolomics links the loss of the mitochondrial folate enzyme to deregulation of a lipid metabolism observed in rare human disorder.Human genomics · 2020Article
- Cytosolic 10-formyltetrahydrofolate dehydrogenase regulates glycine metabolism in mouse liver.Scientific reports · 2019Article
- Loss of ALDH1L1 folate enzyme confers a selective metabolic advantage for tumor progression.Chemico-biological interactions · 2019Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ALDH1L1 is a folate-metabolizing enzyme abundant in liver and several other tissues. In human cancers and cell lines derived from malignant tumors, the ALDH1L1 gene is commonly silenced through the promoter methylation. It was suggested that ALDH1L1 limits proliferation capacity of the cell and thus functions as putative tumor suppressor. In contrast to cancer cells, mouse cell lines NIH3T3 and AML12 do express the ALDH1L1 protein. In the present study, we show that the levels of ALDH1L1 in these cell lines fluctuate throughout the cell cycle. During S-phase, ALDH1L1 is markedly down regulated at the protein level. As the cell cultures become confluent and cells experience increased contact inhibition, ALDH1L1 accumulates in the cells. In agreement with this finding, NIH3T3 cells arrested in G1/S-phase by a thymidine block completely lose the ALDH1L1 protein. Treatment with the proteasome inhibitor MG-132 prevents such loss in proliferating NIH3T3 cells, suggesting the proteasomal degradation of the ALDH1L1 protein. The co-localization of ALDH1L1 with proteasomes, demonstrated by confocal microscopy, supports this mechanism. We further show that ALDH1L1 interacts with the chaperone-dependent E3 ligase CHIP, which plays a key role in the ALDH1L1 ubiquitination and degradation. In NIH3T3 cells, silencing of CHIP by siRNA halts, while transient expression of CHIP promotes, the ALDH1L1 loss. The downregulation of ALDH1L1 is associated with the accumulation of the ALDH1L1 substrate 10-formyltetrahydrofolate, which is required for de novo purine biosynthesis, a key pathway activated in S-phase. Overall, our data indicate that CHIP-mediated proteasomal degradation of ALDH1L1 facilitates cellular proliferation.
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