ArticleGenes & development2013
A RANKL-PKCβ-TFEB signaling cascade is necessary for lysosomal biogenesis in osteoclasts.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 176 citations in OpenAlex.
- Temporal transcriptomic profiling uncovers multilevel suppression of RANKL-driven osteoclast differentiation by 14-3-3ζ.The Journal of biological chemistry · 2026Article
- Wogonin, a bioactive flavonoid from Scutellaria baicalensis, alleviates alcoholic pancreatitis via AMPK-mediated TFEB activation.Journal of advanced research · 2026Article
- A comprehensive in silico investigation into the deleterious nonsynonymous single nucleotide polymorphisms of the human transcription factor EB (TFEB) gene and their predicted association with cancer.Journal, genetic engineering & biotechnology · 2026Article
- AMPK promotes TFEB transcriptional activity through dephosphorylation at both MTORC1-dependent and -independent sites.Autophagy · 2026Article
- Identification of KHS-101 as a Transcription Factor EB Activator to Promote α-Synuclein Degradation.International journal of molecular sciences · 2026Article
- Circadian regulation of osteoclast lysosomal-resorption machinery: implications for osteoporosis therapy.Frontiers in cell and developmental biology · 2026Review
- cAMP promotes acute lysosome biogenesis through TFEB nuclear import-export dynamics.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of virally induced TFEB proteasomal degradation as a host-centric therapeutic approach for coronaviral infection.Science advances · 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
- Evolutionary conserved regulation of TFEB stability by the E3 ubiquitin ligase WWP2 modulates response to stressiScience · 2025Article
- Bidirectional crosstalk between the bone extracellular matrix and lysosomes in bone remodeling and osteoporosis.Frontiers in endocrinology · 2025Review
- Lysosome-Iron-Mitochondria Axis in Osteoclasts: Iron as a Central Player.Research (Washington, D.C.) · 2025Review
- Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity.The Journal of cell biology · 2024Article
- Regulation of Caenorhabditis elegans HLH-30 subcellular localization dynamics: Evidence for a redox-dependent mechanism.Free radical biology & medicine · 2024Article
- Lysosome quality control in health and neurodegenerative diseases.Cellular & molecular biology letters · 2024Review
- Rejuvenation of BMSCs senescence by pharmacological enhancement of TFEB-mediated autophagy alleviates aged-related bone loss and extends lifespan in middle aged mice.Bone research · 2024Article
- TFEB activation hallmarks antigenic experience of B lymphocytes and directs germinal center fate decisions.Nature communications · 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
- Sirtuins Affect Cancer Stem Cells via Epigenetic Regulation of Autophagy.Biomedicines · 2024Review
69 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 6 institutions in 4 countries.
Funding
Abstract
Bone resorption by osteoclasts requires a large number of lysosomes that release proteases in the resorption lacuna. Whether lysosomal biogenesis is a consequence of the action of transcriptional regulators of osteoclast differentiation or is under the control of a different and specific transcriptional pathway remains unknown. We show here, through cell-based assays and cell-specific gene deletion experiments in mice, that the osteoclast differentiation factor RANKL promotes lysosomal biogenesis once osteoclasts are differentiated through the selective activation of TFEB, a member of the MITF/TFE family of transcription factors. This occurs following PKCβ phosphorylation of TFEB on three serine residues located in its last 15 amino acids. This post-translational modification stabilizes and increases the activity of this transcription factor. Supporting these biochemical observations, mice lacking in osteoclasts--either TFEB or PKCβ--show decreased lysosomal gene expression and increased bone mass. Altogether, these results uncover a RANKL-dependent signaling pathway taking place in differentiated osteoclasts and culminating in the activation of TFEB to enhance lysosomal biogenesis-a necessary step for proper bone resorption.
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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.