The U-box-type ubiquitin ligase PRP19β regulates astrocyte differentiation via ubiquitination of PTP1B

Yamada, Takeyuki; Urano-Tashiro, Yumiko; Hashi, Yoshimi; Sakumoto, Marimu; Akiyama, Hirotada; Tashiro, Fumio

doi:10.1016/j.brainres.2013.06.007

Cited by 14 publications

(10 citation statements)

References 39 publications

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“…Compelling recent findings suggest PTP1B holds potential as a therapeutic target in AD. Results indicate that PTP1B regulates distinct CNS responses depending on cell type: while PTP1B modulates insulin and leptin signaling in neurons, it regulates astrocyte differentiation (Yamada et al, 2013 ) and proinflammatory responses in microglia. Because PTP1B participates in several cellular/molecular processes linked to AD pathogenesis (Figure 1 ), compounds capable of reaching the CNS and inhibiting PTP1B activity in neurons and/or glial cells may rescue multiple aberrant processes associated with cognitive decline and neurodegeneration in AD.…”

Section: Discussionmentioning

confidence: 99%

Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer’s Therapy?

Vieira

Silva

Ferreira

et al. 2017

Front. Aging Neurosci.

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Despite significant advances in current understanding of mechanisms of pathogenesis in Alzheimer’s disease (AD), attempts at drug development based on those discoveries have failed to translate into effective, disease-modifying therapies. AD is a complex and multifactorial disease comprising a range of aberrant cellular/molecular processes taking part in different cell types and brain regions. As a consequence, therapeutics for AD should be able to block or compensate multiple abnormal pathological events. Here, we examine recent evidence that inhibition of protein tyrosine phosphatase 1B (PTP1B) may represent a promising strategy to combat a variety of AD-related detrimental processes. Besides its well described role as a negative regulator of insulin and leptin signaling, PTB1B recently emerged as a modulator of various other processes in the central nervous system (CNS) that are also implicated in AD. These include signaling pathways germane to learning and memory, regulation of synapse dynamics, endoplasmic reticulum (ER) stress and microglia-mediated neuroinflammation. We propose that PTP1B inhibition may represent an attractive and yet unexplored therapeutic approach to correct aberrant signaling pathways linked to AD.

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Section: Discussionmentioning

confidence: 99%

Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer’s Therapy?

Vieira

Silva

Ferreira

et al. 2017

Front. Aging Neurosci.

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“…In a similar fashion, the neuronspecific tyrosine phosphatase protein-tyrosine phosphatase 1B (PTP1B) knockout mice are overresponsive to the effects of exogenous leptin and show reduced adiposity and elevated energy expenditure with activity [48]. PTP1B may influence astrocyte migration and differentiation, mediating some of leptin's effects on neural development discussed below [49,50]. These data suggest that both SOCS3 and PTP1B are mediators that may lead to reduced LepRb signaling in obesity and influence brain functioning, although further mechanisms remain to be determined.…”

mentioning

confidence: 94%

Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

2015

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“…The ubiquitin-proteasome system, catalyzed by E1, E2, and E3 enzymes, is a method for getting rid of proteins (Ciechanover, 2003(Ciechanover, , 2005. The ectopic expression of ubiquitin ligase PRP19β (precursor RNA processing-19β) regulates astrocyte differentiation through the ubiquitination of PTP1B and phosphorylation of STAT3 (Yamada et al, 2013). The family of TRIM-containing protein is a subfamily of E3 that regulates diabetes mellitus complications such as TRIM13 and TRIM16 (Li et al, 2017(Li et al, , 2020.…”

Section: Introductionmentioning

confidence: 99%

TRIM18-Regulated STAT3 Signaling Pathway via PTP1B Promotes Renal Epithelial–Mesenchymal Transition, Inflammation, and Fibrosis in Diabetic Kidney Disease

et al. 2021

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Diabetic kidney disease (DKD) has become a key cause of end-stage renal disease worldwide. Inflammation and fibrosis have been shown to play important roles in the pathogenesis of DKD. MID1, also known as TRIM18, is an E3 ubiquitin ligase of the tripartite motif (TRIM) subfamily of RING-containing proteins and increased in renal tubule in patients with DKD. However, the function and molecular mechanism of TRIM18 in DKD remain unexplored. Herein we report that TRIM18 expression levels were increased in patients with DKD. An animal study confirms that TRIM18 is involved in kidney injury and fibrosis in diabetic mice. TRIM18 knockdown inhibits high glucose (HG)-induced epithelial–mesenchymal transition (EMT), inflammation, and fibrosis of HK-2 cells. This is accompanied by decreased levels of tumor necrosis factor alpha, interleukin-6, hydroxyproline (Hyp), connective tissue growth factor, and α-smooth muscle actin. Additionally, TRIM18 knockdown inhibits HG-induced increase in the phosphorylated-/total signal transducer and activator of transcription (STAT3). Treatment with niclosamide (STAT3 inhibitor) or protein tyrosine phosphatase-1B (PTP1B) overexpression blocked the TRIM18 induced EMT, inflammation and fibrosis. Co-immunoprecipitation and Western blot assays showed that TRIM18 promoted the ubiquitination of PTP1B. These findings highlight the importance of the TRIM18/PTP1B/STAT3 signaling pathway in DKD and can help in the development of new therapeutics for DKD treatment.

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The U-box-type ubiquitin ligase PRP19β regulates astrocyte differentiation via ubiquitination of PTP1B

Cited by 14 publications

References 39 publications

Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer’s Therapy?

Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer’s Therapy?

Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

TRIM18-Regulated STAT3 Signaling Pathway via PTP1B Promotes Renal Epithelial–Mesenchymal Transition, Inflammation, and Fibrosis in Diabetic Kidney Disease

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