Ubiquitin-Binding Protein p62 Expression Is Induced during Apoptosis and Proteasomal Inhibition in Neuronal Cells
Abstract
Neuronal apoptosis is involved in several pathological conditions of the brain. Using cDNA arrays, we observed upregulation of ubiquitin-binding protein p62 expression during serum withdrawal-induced apoptosis in Neuro-2a cells. We demonstrate here that the expression levels of p62 mRNA and protein were increased in Neuro-2a cells and cultured rat hippocampal neurons by different types of proapoptotic treatments, including serum deprivation, okadaic acid, etoposide, and trichostatin A. Ubiquitin-binding protein p62 is a widely expressed cytoplasmic protein of unclear function. The ability of p62 to bind noncovalently to ubiquitin and to several signalling proteins suggests that p62 may play a regulatory role connected to the ubiquitin system. Accordingly, we show that proteasomal inhibitors MG-132, lactacystin, and PSI caused a prominent upregulation of p62 mRNA and protein expression, with a concomitant increase in ubiquitinated proteins. To conclude, p62 upregulation appears to be a common event in neuronal apoptosis. Results also suggest that the induction of p62 expression by proteasomal inhibitors may be a response to elevated levels of ubiquitinated proteins, possibly constituting a protective mechanism.
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SQSTM1 is a major component of neuronal and glial cytoplasmic inclusions in Alzheimer disease and Parkinson disease.
“SQSTM1 is a major component of neuronal and glial cytoplasmic inclusions that characterize many neurological disorders such as Alzheimer disease and Parkinson disease [114,115].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [114]
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- Authors
- Kuusisto, E., Suuronen, T., & Salminen, A.
- Affiliations
- University of Eastern Finland (FI)
- ORCID
- Salminen, Antero
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 280
- Issue
- 1
- Pages
- 223-228
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2058231034
- Cited by
- 131
- References
- 22
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 5 · 2015: 2 · 2014: 7 · 2013: 15 · 2012: 10
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- p62, ubiquitin-binding protein, neuronal apoptosis, proteasome inhibition, ubiquitin system, ubiquitinated proteins, serum deprivation, hippocampal neurons, N2a cells, MG132, lactacystin, extrasensory perception, okadaic acid, etoposide, trichostatin A, neuroprotection
- MeSH terms
- Animals, Carrier Proteins, Cells, Cultured, Cysteine Endopeptidases, Etoposide, Gene Expression Regulation, Hippocampus, Hydroxamic Acids, Multienzyme Complexes, Neuroblastoma, Neurons, RNA, Messenger, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured, Culture Media, Serum-Free, Apoptosis, Immediate-Early Proteins, Okadaic Acid, Proteasome Endopeptidase Complex, Mice, Rats, Transcription Factor TFIIH
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