Disease relevance of ID1

• Immunohistochemical analysis showed that ID1 was highly expressed by (myo)fibroblasts within fibrotic foci in experimentally induced pulmonary fibrosis [1].
• Treatments with 12-O-tetradecanoylphorbol-13-acetate, another inducer of neuroblastoma cell differentiation, also resulted in coordinated down-regulation of ID gene expression, underscoring the role of ID genes in differentiation [2].
• In conclusion, our study supports a significant role of the ID1 protein in melanoma progression and patient prognosis [3].
• The clinical events with the highest ID1 were dyspepsia (25.4 per 1000 pme) followed by abdominal pain (10.6) [4].
• The events reported with the highest ID1 were malaise/lassitude (14.6), dizziness (12.2), cardiac failure (9.7), dyspnea (9.7) and hypotension (8.5) [5].

Psychiatry related information on ID1

• From the panel of differentially expressed genes, ID1 (inhibitor of differentiation 1) was considered to be particularly relevant to the pathogenesis of RA, because Id family genes have been shown to play a role in cell proliferation and angiogenesis [6].
• In this study, human male germ cell tumors (GCTs) were used as a model for examining the expression of the ID genes in various histologies that are reflective of different temporal phases of human development [7].

High impact information on ID1

• Similar studies with the endonuclease MspI revealed alleles of many different sizes (the difference was due to an insertion-deletion polymorphism), which we grouped as larger and smaller alleles and designated as ID1 and ID2, respectively [8].
• Because of their involvement in cell differentiation and neural development, ID genes are ideal primary targets for MeCP2 regulation of neuronal maturation that may explain the molecular pathogenesis of RTT [9].
• Localization of the Usher syndrome type ID gene (Ush1D) to chromosome 10 [10].
• Interactions between ID and OLIG proteins mediate the inhibitory effects of BMP4 on oligodendroglial differentiation [11].
• By contrast, ID1 and ID3 did not complex with the OLIG proteins [11].

Biological context of ID1

• ID1 acts as a dominant-negative antagonist of basic helix-loop-helix transcription factors that drive cell lineage commitment and differentiation [1].
• ID1 further behaved like a typical immediate-early gene and, unlike ID3, was expressed and induced at the protein level [1].
• Down-regulation of ID gene expression by RA involves a complex mechanism because full transcriptional repression required newly synthesized proteins and signaling by phosphatidylinositol 3-kinase (PI3K) [2].
• To test the relevance of this upregulation, ID1 and ID2 were overexpressed in NB4 cells [12].
• Since ID1 has been shown to be crucial for cell cycle control, we propose that GDF5 could be involved in the process of angiogenesis [13].

Anatomical context of ID1

• Treatment of cultured neural progenitor cells with BMP4 induced expression of all four members of the inhibitor of differentiation (ID) family of helix-loop-helix transcriptional inhibitors and blocked oligodendrocyte (OL) lineage commitment [11].
• Expression of ID family genes in the synovia from patients with rheumatoid arthritis [6].
• ATRA induced a rapid increase in ID1 and ID2, both in the APL cell line NB4 as well as in primary patient cells [12].
• The objective of this study was, therefore, to characterize the signal transduction pathway of GDF5, especially the involvement of ID1, in human umbilical vein smooth muscle cells (HUVSMC) [13].
• Overexpression of the ID proteins in normal human keratinocytes results in extension of culture lifespan, indicating that these proteins are important for epidermal differentiation [14].

Associations of ID1 with chemical compounds

• These results indicate that ID1 and ID2 are important retinoic acid responsive genes in APL, and suggest that the inhibition of specific bHLH transcription factor complexes may play a role in the therapeutic effect of ATRA in APL [12].
• The specific inhibitor of p38 MAPK or ERK, SB203580 or U0126 did not induce ID protein expression [13].
• The relevance of these findings was further studied after interfering p53 expression in MCF7 cells (shp53 cells), showing a lower induction of both, ID1 and ID2 transcripts, after 5-FU when compared with MCF7 shGFP control cells [15].
• Indeed, teleostean ID1 is conspicuously resistant to propylthiouracil (PTU) inhibition, and its response to thyroidal status differs from that exhibited by other ID1s [16].
• ID1 expression was also increased by dimethylnitrosamine, acetylaminofluorene and acetaminophen in both primary hepatocytes and HepG2 [17].

Physical interactions of ID1

• Expression of the helix-loop-helix protein inhibitor of DNA binding-1 (ID-1) is activated by all-trans retinoic acid in normal human keratinocytes [14].
• Functional analysis suggests that only ID1 may work as a pore-occluding ball domain, whereas ID2 most likely acts as a "docking domain" that attaches ID1 to the cytoplasmic face of the channel [18].

Regulatory relationships of ID1

• Smad1 siRNA transfection inhibited the upregulation of ID protein [13].
• The absence of correlation with p16 protein expression and angiogenesis suggests that other regulatory pathways and mechanisms might be influenced by ID1 in melanomas [3].

Other interactions of ID1

• We show that the mRNA levels of the differentiation-inhibiting basic helix-loop-helix transcription factors ID1, ID2, and ID3 are down-regulated during RA-induced differentiation of SH-SY5Y cells [2].
• Here we report the identification of two ATRA responsive genes in APL cells, ID1 and ID2 [12].
• ID1 and ID2 are retinoic acid responsive genes and induce a G0/G1 accumulation in acute promyelocytic leukemia cells [12].
• GDF5 had chemotactic activity in HUVSMC; this effect was partly blocked by transfection of smad1 or ID1 siRNA [13].
• We selected four genes (DOC1, KLF4, TC-1, ID1) from the microarray profile that showed a similar pattern of expression for both of the antiangiogenic agents we tested [19].

Analytical, diagnostic and therapeutic context of ID1

• All four ID proteins were significantly increased in Mecp2-deficient mouse and human RTT brain using immunofluorescence and laser scanning cytometric analyses [9].
• We show, by somatic cell hybridization and fluorescence in situ hybridization experiments, that ID1 and ID2 are localized at 20q11 and 2p25, respectively [20].
• To examine BMP target genes, the mRNA expression of ID1, ID3, and MSX2 was determined by quantitative real-time PCR [21].
• To evaluate the importance of ID1 in malignant melanoma, tumour cell expression was examined by immunohistochemistry in 119 cases of nodular melanoma using tissue microarray technique, and related to multiple tumour markers including proliferation, p16 expression, angiogenesis and patient survival [3].
• Immunoblotting confirmed that ID1 induction was more extensive and sustained in p53(+) cells [22].

References