ArticleThe Journal of cell biology2020
CDK4/6 regulate lysosome biogenesis through TFEB/TFE3.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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The trial behind it
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Who cites it
64 citing papers in PubMed, 99 citations in OpenAlex.
- Disrupted TFEB/GDNF-cAMP/ATP Coupling Underlies Astrocytic Dysfunction and Depression in LRRK2 G2019S Parkinson's Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Time-resolved proteomic and phosphoproteomic analysis reveals convergent and divergent biological perturbations induced by FDA-approved CDK4/6 inhibitors in hormone receptor-positive breast cancers.Acta pharmacologica Sinica · 2026Article
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- TFEB degradation is regulated by an IKK/β-TrCP2 phosphorylation-ubiquitination cascade.Nature communications · 2026Article
- Review
- Lysosomal membrane homeostasis and its importance in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Metformin sensitizes non-small cell lung cancer to CDK4/6 inhibitor treatment by reducing lysosomal trapping.Science China. Life sciences · 2026Article
- TFE3 fusion proteins promoted the progression of Xp11.2 translocation renal cell carcinoma through post-translational modification of PDL1 by upregulating CCND1/Cyclin D1.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Targeting RBM10-Repressed RORB Activity in Liquid Condensates Inhibits Lysosomal Biogenesis and Neuroblastoma Progression via Affecting NF-κB Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Investigation of dynamic regulation of TFEB nuclear shuttling by microfluidics and quantitative modelling.Communications biology · 2025Article
- Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR.International journal of molecular medicine · 2025Article
- CDK4/6 inhibition initiates cell cycle arrest by nuclear translocation of RB and induces a multistep molecular response.Cell death discovery · 2024Article
- CDK4/6 Inhibitors Impede Chemoresistance and Inhibit Tumor Growth of Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Feedforward cysteine regulation maintains melanoma differentiation state and limits metastatic spread.Cell reports · 2024Article
- Abemaciclib and Vacuolin-1 decrease aggregate-prone TDP-43 accumulation by accelerating autophagic flux.Biochemistry and biophysics reports · 2024Article
- Golgi dispersal in cancer stem cells promotes chemoresistance of colorectal cancer via the Golgi stress response.Cell death & disease · 2024Article
- Exploring lysosomal biology: current approaches and methods.Biophysics reports · 2024Article
- Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology.Nature reviews. Molecular cell biology · 2024Review
- From the regulatory mechanism of TFEB to its therapeutic implications.Cell death discovery · 2024Review
- Hexamethylene amiloride synergizes with venetoclax to induce lysosome-dependent cell death in acute myeloid leukemia.iScience · 2024Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomes are degradation and signaling organelles that adapt their biogenesis to meet many different cellular demands; however, it is unknown how lysosomes change their numbers for cell division. Here, we report that the cyclin-dependent kinases CDK4/6 regulate lysosome biogenesis during the cell cycle. Chemical or genetic inactivation of CDK4/6 increases lysosomal numbers by activating the lysosome and autophagy transcription factors TFEB and TFE3. CDK4/6 interact with and phosphorylate TFEB/TFE3 in the nucleus, thereby inactivating them by promoting their shuttling to the cytoplasm. During the cell cycle, lysosome numbers increase in S and G2/M phases when cyclin D turnover diminishes CDK4/6 activity. These findings not only uncover the molecular events that direct the nuclear export of TFEB/TFE3, but also suggest a mechanism that controls lysosome biogenesis in the cell cycle. CDK4/6 inhibitors promote autophagy and lysosome-dependent degradation, which has important implications for the therapy of cancer and lysosome-related disorders.
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Registered trials
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.