• Journal of the Korea Academia-Industrial cooperation Society
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• 제10권3호
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• pp.648-653
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• 2009

p62 is a key component of protein aggregates found in brains of neurodegenerative diseases in which oxidative stress is involved in the pathogenesis. p62 was induced in SH-SY5Y, a neuroblastoma cell line, by hydroxydoparnine or $C_2-ceramide$ known to be related to neurodegenerative diseases. The over-expression of p62 showed the neuroprotective effect against the ceramide induced cell death. In addition, p62 became insoluble and cleaved forms as time proceeded after the ceramide treatment, suggesting the mechanism by which p62 is associated with aggregates in neurodegenerative diseases.

• Development and Reproduction
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• 제2권2호
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• pp.165-171
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• 1998

p62 is a novel cytoplsmic protein that binds to SH2 domain of p56$^{lck}$, lymphocyte-specific protein tyrosine kinase, and the expression of p62 was observed in most tissues. In addition p62 interacts with various proteins including ubiquitin and atypical PKC isoform, indicating its diverse biological role in different tissues. However, little is known about functional connection between p62 and its binding proteins. In the present study, a novel cellular protein, p62 has been shown to bind to 14-3-3 $\tau$ isoform that is specific for T cells. Moreover, overexpression of p62 in T cells caused to delay onset of UV-induced apoptosis characterized by DNA fragmentation and breakdown of poly (ADP-ribose) polymerase (PARP). Lately, 14-3-3 proteins have been shown to mediate survival signal via interacting proapoptotic Bad protein in the Iymphocyte. These results suggested the presence of p62-mediated regulatory mechanism during apoptosis in T cells, in which activation-induced apoptotic signal could be interfered by p62 and 14-3-3 protein.n.

• Animal cells and systems
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• 제5권2호
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• pp.145-151
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• 2001

p62 is a phosphotyrosine-independent ligand of the SH2 domain of $p56^{Ick}$, a T-cell specific Src family tyrosine kinase. Recently p62 has been shown to interact with a number of proteins, such as $PKC\varsigma$ and ubiquitin, and implicated in important cellular functions such as cell proliferation. Since the two p62 interacting proteins, $p56^{Ick}$ and $PKC\varsigma$, have been reported to play roles in cell death, 1 have addressed the potential role of p62 during apoptosis in Jurkat cells in this study. Herein 1 show that p62 was specifically cleaved into two peptides by a caspase-3-like activity during Fas-receptor mediated apoptosis in Jurkat cells. This cleavage generated two fragments with molecular weights of about 35 kDa that differed in subcellular localizations. The N-terminal cleaved fragment was present in the detergent-insoluble fraction whereas the C-terminal fragment was found in the detergent-soluble fraction. In addition, the C-terminal fragment appeared to be subjected to further degradation as apoptosis prolonged. Moreover, overexpression of p62 in Jurkat cells attenuated the Fas receptor mediated apoptosis, suggesting that p62 is involved in apoptotic signal transduction pathway in lymphocytes.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4095-4099
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• 2013

Oxidative stress induces apoptosis in many cellular systems including glioblastoma cells, with caspase-8 activation was regarded as a major contribution to $H_2O_2$-induced cell death. This study focused on the role of the autophagic protein p62 in $H_2O_2$-induced apoptosis in U87MG cells. Oxidative stress was applied with $H_2O_2$, and cell apoptosis and viability were measured with use of caspase inhibitors or autophagic mediators or siRNA p62, GFP-p62 and GFP-p62-UBA (del) transfection. We found that $H_2O_2$-induced U87MG cell death was correlated with caspase-8. To understand the role of p62 in MG132-induced cell death, the levels of p62/SQSTM1 or autophagy in U87MG cells were modulated with biochemical or genetic methods. The results showed that the over-expression of wild type p62/SQSTM1 significantly reduced $H_2O_2$ induced cell death, but knockdown of p62 aggravated the process. In addition, inhibition of autophagy promoted p62 and active caspase-8 increasing $H_2O_2$-induced apoptosis while induction of autophagy manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 required its C-terminus UBA domain to attenuate $H_2O_2$ cytotoxity by inhibition of caspase-8 activity. Our results indicated that p62/SQSTM1 was a potential contributor to mediate caspase-8 activation by autophagy in oxidative stress process.

• Korean Journal of Plant Resources
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• 제36권4호
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• pp.275-281
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• 2023

Autophagy contributes to enhancing the immune system (innate and adaptive immune system) against foreign pathogens. Autophagy of macrophages is used as a major indicator for developing vaccine adjuvants to increase the adaptive immune response. In this study, PLR activated autophagy and increased p62/SQSTM1. The knockdown of p62/SQSTM1 attenuated PLR-mediated autophagy. Inhibition of TLR4 blocked PLR-mediated increase in p62/SQSTM1 level and autophagy induction. In addition, inhibition of PI3K blocked HSL-mediated increase of p62/SQSTM1. PLR increased Nrf2 level and the inhibition of TLR4 and PI3K reduced PLR-mediated increase of Nrf2. Taken together, it is believed that PLR may induce autophagy through upregulating p62/SQSTM1 via TLR4/PI3K/Nrf2 signaling pathway.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.195-204
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• 2021

Cereblon (CRBN), a substrate receptor of cullin 4-RING E3 ligase (CRL4) regulates the ubiquitination and degradation of c-Jun, mediating the lipopolysaccharide-induced cellular response. However, the upstream signaling pathway that regulates this process is unknown. In this study, we describe how endoplasmic reticulum (ER) stress reversely regulates sequestosome-1 (p62)and c-Jun protein levels. Furthermore, our study reveals that expression of p62 attenuates c-Jun protein levels through the ubiquitinproteasome system. Conversely, siRNA knockdown of p62 elevates c-Jun protein levels. Immunoprecipitation and immunoblotting experiments demonstrate that p62 interacts with c-Jun and CRBN to form a ternary protein complex. Moreover, we find that CRBN knockdown completely abolishes the inhibitory effect of p62 on c-Jun. Using brefeldin A as an inducer of ER stress, we demonstrate that the p62/c-Jun axis participates in the regulation of ER stress-induced apoptosis, and that CRBN is required for this regulation. In summary, we have identified an upstream signaling pathway, which regulates p62-mediated c-Jun degradation. Our findings elucidate the underlying molecular mechanism by which p62/c-Jun axis regulates the ER stress-induced apoptosis, and provide a new molecular connection between ER stress and apoptosis.

• Journal of Yeungnam Medical Science
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• 제12권2호
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• pp.210-225
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• 1995

The expression of $p62^{c-myc}$ and $p21^{ras}$ can be seen in many solid tumor, but the pattern and incidence of expression were different according to organ, countries, and examiners, thus it is not definitely defined. Total 67 colorectal carcinoma in paraffin sections are analysed by immunohistochemically for evaluation of the $p62^{c-myc}$ and $p21^{ras}$ expression according to the age, sex, chief complaints, location, differentiation, modified Dukes stage, using the specific monoclonal antibodies. The results were summarized as follows : The age of patients ranged from 32 years to 82 years. The mean age was 57.6 years. The expression of $p62^{c-myc}$ and $p21^{ras}$ was not correlated with age. Male was 29 cases(43.3%) and female was 38 cases(56.7%). The male to female ratio was 1:1.31. The expression of $p21^{ras}$ was increased in female(p<0.05). Abdominal pain(43.7%) was the most frequent chief complaint. The most frequent tumor location was rectum(44.8%). The expression of $p62^{c-myc}$ was increased in the rectum(p<0.05). The 65 cases(97.0%) out of 67 cases showed positive reaction of $p62^{c-myc}$ in the nucleus, cytoplasmic membrane, and cytoplasm. The 62 cases(92.5%) out of 67 cases showed positive reaction of $p21^{ras}$ in the cytoplasmic membrane and cytoplasm. The positive rate of $p62^{c-myc}$ and $p21^{ras}$ was 97.0% and 91.4% in well differentiated adenocarcinoma, 100.0% and 95.0% in moderately differentiated adenocarcinoma, 90.0% and 90.0% in poorly differentiated adenocarcinoma, 100.0% and 100.0% in mucinous carcinoma. The positive rate of $p62^{c-myc}$ and $p21^{ras}$ was 94.1% and 88.2% in Dukes stage $B_1$, 96.0% and 96.0% in Dukes stage $B_2$, 100.0% and 100.0% in Dukes stage $C_1$, 100.0% and 88.9% in Dukes stage $C_2$, and 100.0% and 100.0% in Dukes stage D. The expression of $p62^{c-myc}$ in metastatic colorectal carcinoma showed diffuse and strongly positive reaction than primary colorectal carcinoma. The expression of $p21^{ras}$ in primary colorectal carcinoma showed diffuse and strongly positive reaction than metastatic colorectal carcinoma.

• Food Science of Animal Resources
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• 제41권2호
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• pp.274-287
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• 2021

The purpose of this study is to examine the physiological characteristics and anti-diabetic effects of Pediococcus pentosaceus KI62. The α-amylase and α-glucosidase inhibitory activity of P. pentosaceus KI62 was 94.86±3.30% and 98.59±0.52%, respectively. In MRS broth containing 3% maltodextrin inoculated by P. pentosaceus KI62, the amounts of short chain fatty acids (SCFA) were propionic acid 18.05±1.85 mg/kg, acetic acid 1.12±0.07 g/100 mL, and butyric acid 2.19±0.061 g/kg, and those of medium chain fatty acids (MCFA) were C8 0.262±0.031 mg/kg, C10 0.279±0.021 mg/kg, and C12 0.203±0.009 mg/kg. Compared to sixteen antibiotics, P. pentosaceus KI62 had the highest sensitivity to penicillin-G and rifampicin, as well as the highest resistance to vancomycin and ampicillin. The strain also showed higher leucine arylamidase and valine arylamidase activities than other enzyme activities, but it did not produce β-glucuronidase which is carcinogenic enzymes. The survival rate of P. pentosaceus KI62 in 0.3% bile was 91.67%. Moreover, the strain showed a 98.63% survival rate in pH 2.0. P. pentosaceus KI62 exhibits resistance to Escherichia coli, Salmonella Typhimurium, Listeria monocytogenes, and Staphylococcus aureus at rates of 29.41%, 38.10%, 51.72%, and 50.47%, respectively. P. pentosaceus (23.31%) showed a similar adhesion ability to L. rhamnosus GG, the positive control (24.49%). These results show that P. pentosaceus KI62 has possibility as a probiotic with anti-diabetic effects.

• Biodesign
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• 제6권4호
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• pp.100-102
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• 2018

Autophagy is a degradation pathway that targets many cellular components and plays a particularly important role in protein degradation and recycling. This process is very complex and several proteins participate in this process. One of them, P62/SQSTM1, is related to the N-end rule and induces protein degradation through autophagy. The P62/SQSTM1 makes a huge oligomer, and this oligomerization is known to play an important role in its mechanism. This oligomerization takes two steps. First, the PB1 domain of P62/SQSTM1 makes the base oligomer, and then, when the ligand binds to the ZZ domain of P62/SQSTM1, it induces a higher oligomer by the disulfide bond of the two cysteines. To understand the oligomerization mechanism of P62/SQSTM1, we need to know the dimerization of the PB1 domain. In this study, crystals of PB1 dimer were made and the crystals were diffracted by X-ray to collect usable data up to 3.2A. We are analyzing the structure using the molecular replacement (MR) method.

• Molecules and Cells
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• 제42권10호
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• pp.729-738
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• 2019

Autophagy is an important process for protein recycling. Oligomerization of p62/SQSTM1 is an essential step in this process and is achieved in two steps. Phox and Bem1p (PB1) domains can oligomerize through both basic and acidic surfaces in each molecule. The ZZ-type zinc finger (ZZ) domain binds to target proteins and promotes higher-oligomerization of p62. This mechanism is an important step in routing target proteins to the autophagosome. Here, we determined the crystal structure of the PB1 homo-dimer and modeled the p62 PB1 oligomers. These oligomer models were represented by a cylindrical helix and were compared with the previously determined electron microscopic map of a PB1 oligomer. To accurately compare, we mathematically calculated the lead length and radius of the helical oligomers. Our PB1 oligomer model fits the electron microscopy map and is both bendable and stretchable as a flexible helical filament.