Role of p62/SQSTM1 in liver physiology and pathogenesis

Manley, Sharon; Williams, Jessica A.; Ding, Wen–Xing

doi:10.1177/1535370213489446

Cited by 117 publications

(106 citation statements)

References 152 publications

(469 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These altered forms of the protein were found to localize to non-SG structures, characterized by the presence of ubiquitin and the p62/sequestosome-1 protein (SQSTM1), and the absence of a vimentin cage. SQSTM1 is a scaffold protein containing several protein interaction domains and with multiple functions in signal transduction, cell death and inflammation (54,55). A growing body of evidence suggests in particular a role for p62 in directing ubiquitinated proteins for autophagic destruction, and as a platform for NF-B signaling.…”

Section: Discussionmentioning

confidence: 99%

PARP12, an Interferon-stimulated Gene Involved in the Control of Protein Translation and Inflammation

Welsby

Hutin

Gueydan

et al. 2014

Journal of Biological Chemistry

101

115

View full text Add to dashboard Cite

Background:The individual role of members of the poly(ADP-ribose) polymerase family is unclear. Results: PARP12 displays a dual subcellular localization and effector function, controlling both protein translation and NF-B signaling. Conclusion: PARP12 mediates two important effector mechanisms linked to the establishment of an anti-viral state. Significance: ADP-ribosylation may play an important role in the innate control of microbial infections.

show abstract

Section: Discussionmentioning

confidence: 99%

PARP12, an Interferon-stimulated Gene Involved in the Control of Protein Translation and Inflammation

Welsby

Hutin

Gueydan

et al. 2014

Journal of Biological Chemistry

101

115

View full text Add to dashboard Cite

show abstract

“…Those domains enable p62 to regulate kinase-activated and ubiquitin-mediated signaling pathways [46] . The PB1 domain of p62 interacts with some protein kinases, including ERK1/2, MEKK3 and MEK5 [11] . It has been reported that p62 is involved in regulating ERK1/2 activation.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have suggested that the PB1 domain of p62 interacts with extracellular signal-regulated kinase (ERK) and maintains low ERK activity under normal conditions [11,14,15] . Consistent with these findings, ERK1/2 activity is enhanced in p62-deficient mice [15] .…”

Section: Introductionmentioning

confidence: 99%

“…The ubiquitinated mitochondria are then recognized by p62, which links ubiquitinated substrates/mitochondria to phagophores and leads to the engulfment of the ubiquitinated substrates/mitochondria by phagophores to form autophagosomes [9,10] . As a signaling adaptor protein, p62 has multiple domains [11] and is associated with many diseases. Mutations in the gene encoding p62 lead to Paget's disease of bone (PDB) [12] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Parkin represses 6-hydroxydopamine-induced apoptosis via stabilizing scaffold protein p62 in PC12 cells

Hou

Ren

et al. 2015

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Parkin has been shown to exert protective effects against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in different models of Parkinson disease. In the present study we investigated the molecular mechanisms underlying the neuroprotective action of parkin in vitro. Methods: HEK293, HeLa and PC12 cells were transfected with parkin, parkin mutants, p62 or si-p62. Protein expression and ubiquitination were assessed using immunoblot analysis. Immunoprecipitation assay was performed to identify the interaction between parkin and scaffold protein p62. PC12 and SH-SY5Y cells were treated with 6-OHDA (200 μmol/L), and cell apoptosis was detected using PI and Hoechst staining. Results: In HEK293 cells co-transfected with parkin and p62, parkin was co-immunoprecipitated with p62, and parkin overexpression increased p62 protein levels. In parkin-deficient HeLa cells, transfection with wild-type pakin, but not with ligase activity-deficient pakin mutants, significantly increased p62 levels, suggesting that parkin stabilized p62 through its E3 ligase activity. Transfection with parkin or p62 significantly repressed ERK1/2 phosphorylation in HeLa cells, but transfection with parkin did not repress ERK1/2 phosphorylation in p62-knockdown HeLa cells, suggesting that p62 was involved in parkin-induced inhibition on ERK1/2 phosphorylation. Overexpression of parkin or p62 significantly repressed 6-OHDA-induced ERK1/2 phosphorylation in PC12 cells, and parkin overexpression inhibited 6-OHDA-induced apoptosis in PC12 and SH-SY5Y cells. Conclusion: Parkin protects PC12 cells against 6-OHDA-induced apoptosis via ubiquitinating and stabilizing scaffold protein p62, and repressing ERK1/2 activation.

show abstract

“…Sequestosome 1 (SQSTM1 or p62) is a multifunctional adapter protein. Although the full spectrum of its functions is not known, there is growing evidence that p62 regulates apoptosis and cell survival through the catabolic metabolism of molecules involved in NF-kB, mTOR, MAPK, and possibly also other signaling pathways (4)(5)(6)(7). p62 localizes to the membranes of autophagosomes and is itself cleared by autophagy (6,7).…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic Accumulation of Sequestosome 1 (p62) Is a Predictor of Biochemical Recurrence, Rapid Tumor Cell Proliferation, and Genomic Instability in Prostate Cancer

Burdelski

Reiswich

Hube‐Magg

et al. 2015

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Sequestosome 1 (p62) is a multifunctional adapter protein accumulating in autophagy-defective cells.Experimental Design: To evaluate the clinical impact and relationship with key genomic alterations in prostate cancer, p62 protein levels were analyzed by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Data on ERG status and deletions of PTEN, 3p13, 5q21, and 6q15 were available from earlier studies.Results: p62 immunostaining was absent in benign prostatic glands but present in 73% of 7,822 interpretable prostate cancers. Strong cytoplasmic p62 staining was tightly linked to high Gleason grade, advanced pathologic tumor (pT) stage, positive nodal status, positive resection margin, and early PSA recurrence (P < 0.0001 each). Increased levels of p62 were significantly linked to TMPRSS2-ERG fusions, both by FISH and immunohistochemical analysis (P < 0.0001 each). For example, moderate or strong p62 immunostaining was seen in 28.5% of cancers with TMPRSS2-ERG fusion detected by FISH and in 23.1% of cancers without such rearrangements (P < 0.0001). Strong p62 staining was significantly linked to the presence of all tested deletions, including PTEN (P < 0.0001), 6q15 (P < 0.0001), 5q21 (P ¼ 0.0002), 3p13 (P ¼ 0.0088), and 6q15 (P < 0.0001), suggesting a link between p62 accumulation and loss of genomic stability. The prognostic role of p62 protein accumulation was striking and independent of Gleason grade, pT stage, pN stage, surgical margin status, and preoperative PSA, regardless of whether preoperative or postoperative parameters were used for modeling.Conclusions: Our study identifies cytoplasmic accumulation of p62 as a strong predictor of an adverse prognostic behavior of prostate cancer independently from established clinicopathologic findings.

show abstract

Role of p62/SQSTM1 in liver physiology and pathogenesis

Cited by 117 publications

References 152 publications

PARP12, an Interferon-stimulated Gene Involved in the Control of Protein Translation and Inflammation

PARP12, an Interferon-stimulated Gene Involved in the Control of Protein Translation and Inflammation

Parkin represses 6-hydroxydopamine-induced apoptosis via stabilizing scaffold protein p62 in PC12 cells

Cytoplasmic Accumulation of Sequestosome 1 (p62) Is a Predictor of Biochemical Recurrence, Rapid Tumor Cell Proliferation, and Genomic Instability in Prostate Cancer

Contact Info

Product

Resources

About