ArticlePloS one2021
The SQSTM1/p62 UBA domain regulates Ajuba localisation, degradation and NF-κB signalling function.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 17 citations in OpenAlex.
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- Palmitic Acid Alters Longitudinal Bone Growth While Enhancing Matrix Maturation in an Organotypic Bone Model.Biomolecules · 2026Article
- Moonlighting cytosolic function of ACAD9: suppression of TRAF6-mediated osteoclastogenesis and protection against osteoporosis.Cell death & disease · 2026Article
- The multifaceted role of SQSTM1/p62 in disc degeneration: A master regulator of cellular stress responses.Biochemistry and biophysics reports · 2025Review
- Evidence of an unprecedented cytoplasmic function of DDX11, the Warsaw breakage syndrome DNA helicase, in regulating autophagy.Autophagy · 2025Article
- 14-3-3ζ suppresses RANKL signaling by destabilizing TRAF6.The Journal of biological chemistry · 2024Article
- Lysosomal biogenesis and function in osteoclasts: a comprehensive review.Frontiers in cell and developmental biology · 2024Review
- The combined signatures of programmed cell death and immune landscape provide a prognostic and therapeutic biomarker in the hepatocellular carcinoma.Frontiers in chemistry · 2024Article
- Identification of autophagy-associated circRNAs in sepsis-induced cardiomyopathy of mice.Scientific reports · 2023Article
- Quercetin potentiates the anti-osteoporotic effects of alendronate through modulation of autophagy and apoptosis mechanisms in ovariectomy-induced bone loss rat model.Molecular biology reports · 2023Article
- CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR.Journal of hematology & oncology · 2022Article
- Update on the pathogenesis and genetics of Paget's disease of bone.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The LIM-domain containing protein Ajuba and the scaffold protein SQSTM1/p62 regulate signalling of NF-κB, a transcription factor involved in osteoclast differentiation and survival. The ubiquitin-associated domain of SQSTM1/p62 is frequently mutated in patients with Paget's disease of bone. Here, we report that Ajuba activates NF-κB activity in HEK293 cells, and that co-expression with SQSTM1/p62 inhibits this activation in an UBA domain-dependent manner. SQSTM1/p62 regulates proteins by targeting them to the ubiquitin-proteasome system or the autophagy-lysosome pathway. We show that Ajuba is degraded by autophagy, however co-expression with SQSTM1/p62 (wild type or UBA-deficient) protects Ajuba levels both in cells undergoing autophagy and those exposed to proteasomal stress. Additionally, in unstressed cells co-expression of SQSTM1/p62 reduces the amount of Ajuba present in the nucleus. SQSTM1/p62 with an intact ubiquitin-associated domain forms holding complexes with Ajuba that are not destined for degradation yet inhibit signalling. Thus, in situations with altered levels and localization of SQSTM1/p62 expression, such as osteoclasts in Paget's disease of bone and various cancers, SQSTM1/p62 may compartmentalize Ajuba and thereby impact its cellular functions and disease pathogenesis. In Paget's, ubiquitin-associated domain mutations may lead to increased or prolonged Ajuba-induced NF-κB signalling leading to increased osteoclastogenesis. In cancer, Ajuba expression promotes cell survival. The increased levels of SQSTM1/p62 observed in cancer may enhance Ajuba-mediated cancer cell survival.
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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.