ID2: A negative transcription factor regulating oligodendroglia differentiation

Chen, Xingshu; Zhang, Yuhang; Cai, Qian; Yao, Zhong-Xiang

doi:10.1002/jnr.22826

Cited by 47 publications

(40 citation statements)

References 72 publications

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“…Class V bHLH factors ID1-ID4, interact with E47 and impede the capacity to bind with E-box sequence of E47. [35][36][37] Moreover, CK II, PKA and MAPK-induced phosphorylation suppress E47-mediated transcription activity. 21,[38][39][40] Our results demonstrated E47 as a novel interacting protein of PAK5 that phosphorylated E47 to promote EMT by inhibition of E-cadherin.…”

Section: Discussionmentioning

confidence: 98%

PAK5-mediated E47 phosphorylation promotes epithelial–mesenchymal transition and metastasis of colon cancer

Zhu

Guo

et al. 2015

Oncogene

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The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). However, the relationship between PAK5 and E47 has not been explored. In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation, which decreased cell-cell cohesion, increased cell migration and invasion in vitro and promoted metastasis in a xenograft model. Furthermore, phosphorylation of E47 facilitated its accumulating in nucleus in an importin α-dependent manner, and enhanced E47 binding to E-cadherin promoter directly, leading to inhibition of E-cadherin transcription. In contrast, PAK5-knockdown resulted in blockage of HGF-induced E47 phosphorylation, attenuated association of E47 with importin α and decreased E47 binding to E-cadherin promoter. In addition, we demonstrated a close correlation between PAK5 and phospho-Ser39 E47 expression in colon cancer specimens. More importantly, high expression of phospho-E47 was associated with an aggressive phenotype of colon cancer and nuclear phospho-E47 staining was found in certain cases of colon cancer with metastasis. Collectively, E47 is a novel substrate of PAK5, and PAK5-mediated phosphorylation of E47 promotes EMT and metastasis of colon cancer, suggesting that phosphorylated E47 on Ser39 may be a potential therapeutic target in progressive colon cancer.

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Section: Discussionmentioning

confidence: 98%

PAK5-mediated E47 phosphorylation promotes epithelial–mesenchymal transition and metastasis of colon cancer

Zhu

Guo

et al. 2015

Oncogene

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“…The following negative regulators of oligodendrocyte functioning that we will discuss are inhibitor of DNA binding-2 and -4 (Id2 and Id4) [117,118]. These proteins inhibit oligodendrocyte differentiation by maintaining the oligodendrocytes in their proliferative state.…”

Section: • • Alterations In Gene Expressionmentioning

confidence: 99%

The Role of Oligodendroglial Dysfunction in Amyotrophic Lateral Sclerosis

Nonneman

Robberecht

Bosch

2014

Neurodegen. Dis. Manage.

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Healthy oligodendrocytes are crucial for neurons and abnormal functioning of these cells is involved in several neurodegenerative diseases. We will focus on oligodendroglial pathology in amyotrophic lateral sclerosis (ALS), an adult-onset progressive neurodegenerative disease characterized by selective motor neuron loss. Recent discoveries shed new light on the crucial role of oligodendrocytes in this fatal disease. We will first give an overview of the importance of good-functioning oligodendrocytes for neuronal health, in particular for motor neurons. Subsequently, we will discuss the recent data on oligodendroglial abnormalities in ALS. We conclude that oligodendrocytes should be considered as important contributors to motor neuron degeneration. As a consequence, oligodendrocytes are a promising new therapeutic target for ALS and other neurodegenerative diseases.

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“…Id proteins (Id1-Id4) are helix-loop-helix (HLH) transcription factors highly expressed in the developing CNS (Andres-Barquin et al, 1997). Id proteins inhibit the function of class I basic helix-loop-helix (bHLH) transcription factors (Kee, 2009) and class II tissue-specific bHLH proteins (Chen et al, 2012) by heterodimerization that results in the bHLH factors being unable to bind DNA (Benezra et al, 1990; Andres-Barquin et al, 2000). Transcription factors of the bHLH family direct the proliferation, specification and maturation of multiple neuronal lineages (Atchley and Fitch, 1997; Guillemot, 1999; Ross et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Behavioral abnormalities and Parkinson's-like changes resulting from Id2 inactivation in mice

Havrda

Paolella

Ward

et al. 2013

Disease Models &Amp; Mechanisms

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SUMMARYCharacterizing dopaminergic neuronal development and function in novel genetic animal models might uncover strategies for researchers to develop disease-modifying treatments for neurologic disorders. Id2 is a transcription factor expressed in the developing central nervous system. Id2−/− mice have fewer dopaminergic neurons in the olfactory bulb and reduced olfactory discrimination, a pre-clinical marker of Parkinson’s disease. Here, we summarize behavioral, histological and in vitro molecular biological analyses to determine whether midbrain dopaminergic neurons are affected by Id2 loss. Id2−/− mice were hyperactive at 1 and 3 months of age, but by 6 months showed reduced activity. Id2−/− mice showed age-dependent histological alterations in dopaminergic neurons of the substantia nigra pars compacta (SNpC) associated with changes in locomotor activity. Reduced dopamine transporter (DAT) expression was observed at early ages in Id2−/− mice and DAT expression was dependent on Id2 expression in an in vitro dopaminergic differentiation model. Evidence of neurodegeneration, including activated caspase-3 and glial infiltration, were noted in the SNpC of older Id2−/− mice. These findings document a novel role for Id2 in the maintenance of midbrain dopamine neurons. The Id2−/− mouse should provide unique opportunities to study the progression of neurodegenerative disorders involving the dopamine system.

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ID2: A negative transcription factor regulating oligodendroglia differentiation

Cited by 47 publications

References 72 publications

PAK5-mediated E47 phosphorylation promotes epithelial–mesenchymal transition and metastasis of colon cancer

PAK5-mediated E47 phosphorylation promotes epithelial–mesenchymal transition and metastasis of colon cancer

The Role of Oligodendroglial Dysfunction in Amyotrophic Lateral Sclerosis

Behavioral abnormalities and Parkinson's-like changes resulting from Id2 inactivation in mice

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