Disease relevance of Id3

• RESULTS: The Id3 gene was expressed in the rapidly growing otocyst on embryonic Day 12 and specifically in the fundamental structures of the cochlea, e.g. the organ of Corti, spiral ganglions and stria vascularis, on postnatal Day 1 [1].
• Adenovirus-mediated overexpression of these Id3 isoforms in cultured rat aortic SMCs revealed that infection of SMCs with an adenovirus overexpressing Id3a (in contrast to Id3) resulted in a significant decrease in cell number versus AdLacZ-infected cells [2].

Psychiatry related information on Id3

• We used real-time RT-PCR to examine the effects of these factors on the expression of mRNA encoding the Id proteins, demonstrating an increase in Id2 and Id3 expression in Sertoli cells treated with thyroid hormone, retinoic acid, or testosterone [3].

High impact information on Id3

• Regulation of Id3 cell cycle function by Cdk-2-dependent phosphorylation [4].
• Cdk2-dependent phosphorylation therefore provides a switch during late G1-to-S phase that both nullifies an early G1 cell cycle regulatory function of Id3 and modulates its target bHLH specificity [4].
• We now show that an analogous cell-cycle-regulated phosphorylation of Id3 alters the specificity of Id3 for abrogating both E-box-dependent bHLH homo- or heterodimer complex formation in vitro and E-box-dependent reporter gene function in vivo [4].
• However, at this time, Mash1, Math3, and Id3 expression are all concentrated in the area that specifically gives rise to granule cells and dentate precursor cells [5].
• In contrast, Id3a stimulates SMC apoptosis and inhibits endogenous Id3 production [6].

Biological context of Id3

• Characterization of inhibitor of differentiation (Id3) gene expression in the developing cochlear tissue of rats [1].
• These results provide evidence that alternative splicing of the Id3 gene may represent an important mechanism by which neointimal SMC growth is attenuated during vascular lesion formation [2].
• Identification of a novel redox-sensitive gene, Id3, which mediates angiotensin II-induced cell growth [7].
• Overexpression of antisense Id3 via transfection in VSMCs completely abolished Ang II- and X/XO-induced cell proliferation [7].

Anatomical context of Id3

• We demonstrate that Id3 is expressed early in lesion formation when the proliferative index of the neointima is highest and that Id3 promotes smooth muscle cell (SMC) proliferation and S-phase entry and inhibits transcription of the cell-cycle inhibitor p21(Cip1) [6].
• CONCLUSION: The Id3 gene is expressed in the developing cochlear tissue and participates in the development of cochlear progenitor hair cells during the embryonic stage [1].
• The effects of Id3 on primary cultures of otocyst epithelial cells and a progenitor hair cell line (OT12) were studied using specific antisense oligonucleotides [1].
• Unlike Id3, Id3a mRNA was not detected in the normal rat carotid artery [2].
• The rapid induction as part of the early response to axonal membranes and cytokines suggested that Id3 is involved in myelin gene repression [8].

Associations of Id3 with chemical compounds

• Intron retention generates a novel Id3 isoform that inhibits vascular lesion formation [6].
• OBJECTIVES: Inhibitor of differentiation (Id3) is an important transcription factor expressed in the cochlear tissue and progenitor hair cells [1].
• The data identified novel androgen-regulated genes (e.g. Id1, Id3, IL-6, IGF-binding protein-2 and -3, and JunB) [9].
• Expression of the helix-loop-helix proteins Id1, Id2 and Id3 was specifically reduced by NGF and this effect was blocked in 5-azacytidine-treated cells, concomitant with the inhibition of NGF-induced neuronal differentiation [10].
• CONCLUSIONS: Ang II induces proliferation of VSMCs via production of superoxide, which enhances the expression of Id3 [7].

Regulatory relationships of Id3

• Ang II, X/XO, and overexpression of sense Id3 downregulated protein expression of p21(WAF1/Cip1), p27(Kip1), and p53 [7].

Other interactions of Id3

• We have recently identified the adult rat pineal gland as a major site of Id-1 and Id-3 expression [11].
• Ang II and overexpression of sense Id3 caused hyperphosphorylation of the retinoblastoma protein [7].
• Overexpression of antisense Id3 abrogated the effect of Ang II on the expression of p21(WAF1/Cip1), p27(Kip1), and p53 [7].

Analytical, diagnostic and therapeutic context of Id3

• MATERIAL AND METHODS: Expression of the Id3 gene in the developing cochlear tissue was examined by means of Northern blotting, in situ hybridization and immunohistochemistry [1].

References