The mechanisms underlying cisplatin resistance in tumors are not fully understood. Previous studies have reported that cellular resistance to oxidative stress is accompanied by resistance to cisplatin. However, the relationship between the resistance to oxidative stress and cisplatin drug resistance in human ovarian cancer cells (HOCCs) is not clear. Here, we reveal a critical role for the mult...

To determine the expression of mTOR, Becline-1, LC3 and p62 in the peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) and assess their relationship with disease activity and immunologic features. The expression of mTOR, Becline-1, LC3 and p62 was detected by RT-PCR in 81 SLE subjects and 86 age- and sex-matched healthy controls. Data regarding demographics and clin...

Genetic, clinical, and neuropathologic heterogeneity have been observed in frontotemporal lobar degeneration with ubiquitin (Ubq)-positive inclusions (FTLD-U) and FTLD-U with motor neuron disease. Here, the distribution and morphologic features of neuronal and glial inclusions in the brains of 20 FTLD-U and 2 FTLD-U/motor neuron disease cases were assessed using immunohistochemistry for Ubq-bin...

The addition of O-linked N-acetylglucosamine (GlcNAc) to the major nuclear pore complex glycoprotein p62 was examined. Expression of the rat p62 cDNA in transfected monkey cells was detected using a rat p62-specific antipeptide antiserum and two previously described nuclear pore-specific monoclonal antibodies which require O-linked GlcNAc for binding. Although the p62 cDNA was predicted to enco...

Suppression of autophagy is always accompanied by marked accumulation of p62, a selective autophagy substrate. Because p62 interacts with the Nrf2-binding site on Keap1, which is a Cullin 3-based ubiquitin ligase adapter protein, autophagy deficiency causes competitive inhibition of the Nrf2-Keap1 interaction, resulting in stabilization of Nrf2 followed by transcriptional activation of Nrf2 tar...

P62 is a synthetic peptide which corresponds to the glycine/alanine repeat sequence of Epstein-Barr virus nuclear antigen-1. It is the main epitope recognised by anti-rheumatoid arthritis nuclear antigen antibodies. It was shown previously that anti-P62 antibodies were raised fourfold in patients with rheumatoid arthritis compared with controls. To examine the possibility that this increase was...

O-linked N-acetylglucosamine (O-GlcNAc) modification has been described in many proteins, including nuclear pore glycoproteins. In the present study we investigated the effect of extracellular glucose on the level of modification of nuclear pore protein p62 by O-GlcNAc. We found that exposure of cells to a high concentration of glucose caused an increased level of modification of p62 with O-Glc...

Acquired resistance to doxorubicin in breast cancer is a serious therapeutic problem. In this study, we investigated whether Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) could inhibit the growth of doxorubicin-resistant breast cancer cells. We found that the expressions of Nrf2 and p62 in breast cancer were higher than that in the corresponding adjacent normal tissues and be...

Promoting cell death by autophagy could be a novel treatment for cancer. The major player in autophagy, p62, serves as a good therapeutic target. Ginkgetin, a biflavonoid from Ginkgo biloba leaves, exhibited promising anticancer activity in non-small cell lung cancer cell lines, with an IC50 lower than that of cisplatin. This anticancer effect of ginkgetin was illustrated in a xenograft nude mo...

Inclusions isolated from several neurodegenerative diseases, including Alzheimer's disease (AD), are characterized by ubiquitin-positive proteinaceous aggregates. Employing confocal and immunoelectron microscopy, we find that the ubiquitin-associating protein sequestosome1/p62, co-localizes to aggregates isolated from AD but not control brain, along with the E3 ubiquitin ligase, TRAF6. This int...