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Id Proteins (id + protein)
Selected AbstractsLong-term effects of idiotype vaccination on the specific T-cell response in peripheral blood and bone marrow of multiple myeloma patientsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2007Amir Osman Abdalla Abstract Objectives:, To elucidate long-term effects of idiotype (Id) vaccination on Id-specific T cells of multiple myeloma (MM) patients and compare Id-specific T-cell responses of peripheral blood with those of bone marrow (BM). Materials and methods:, Id-specific T-cell responses of peripheral blood mononuclear cells (PBMC) were compared with those of BM mononuclear cells (BMMC) in 10 MM patients vaccinated with the Id protein at a median time of 41 months since the last immunization. The PBMC responses at late follow-up were also compared with those during active immunization. The responses were assessed by a proliferation assay, enzyme-linked immunospot (ELISPOT) (,-interferon), cytometric bead array (CBA) for secreted cytokines and quantitative real-time polymerase chain reaction (QRT-PCR) for cytokine gene expression. Results:, At the late testing time, an Id-specific response was detected in PBMC of five patients (ELISPOT, CBA, QRT-PCR) and in BMMC of four patients (CBA, QRT-PCR). A response in both compartments was noted only in three patients. The cytokines gene profile was consistent with a predominance of Th2 cells [interleukin (IL)-4, IL-5, IL-10]. Comparison of the Id-specific responses of PBMC during active immunization with those at the late follow-up showed that the frequency and magnitude of the responses had decreased significantly by time (proliferation/ELISPOT) (P < 0.02) and shifted at the gene level from a Th1 to a Th2 profile (P < 0.05). Conclusion:, Id-specific T cells may decline overtime and shift toward a Th2 response and may be found at a similar frequency of patients in blood and BM. [source] Id2, Id3, and Id4 proteins show dynamic changes in expression during vibrissae follicle developmentDEVELOPMENTAL DYNAMICS, Issue 6 2008Nigel L. Hammond Abstract Id proteins are involved in the transcriptional control of many fundamental biological processes, including differentiation and lineage commitment. We studied Id2, Id3, and Id4 protein expression during different stages of rat vibrissa follicle development using immunohistochemistry. Id2 was highly expressed in the cytoplasm of specialized cells in the basal epidermis and outer root sheath during early stages of follicle development. These cells were identified as Merkel cells (MCs) by means of double-immunolabeling with synaptophysin and cytokeratin-20, and persisted in neonatal follicles. Id3 immunofluorescence was characterized by membrane-associated expression in basal epithelial cells of follicles early in development. Subsequently follicle epithelial cells switched to have strong nuclear labeling, also a feature of newly forming dermal papilla cells. Id4 expression was primarily associated with innervation of the developing follicle musculature. These observations illustrate dynamic expression patterns of Id2 and Id3 proteins in developing follicles and specifically link Id2 expression to Merkel cell specification. Developmental Dynamics 237:1653,1661, 2008. © 2008 Wiley-Liss, Inc. [source] Two major Smad pathways in TGF-, superfamily signallingGENES TO CELLS, Issue 12 2002Keiji Miyazawa Members of the transforming growth factor-, (TGF-,) superfamily bind to two different serine/threonine kinase receptors, i.e. type I and type II receptors. Upon ligand binding, type I receptors specifically activate intracellular Smad proteins. R-Smads are direct substrates of type I receptors; Smads 2 and 3 are specifically activated by activin/nodal and TGF-, type I receptors, whereas Smads 1, 5 and 8 are activated by BMP type I receptors. Nearly 30 proteins have been identified as members of the TGF-, superfamily in mammals, and can be classified based on whether they activate activin/TGF-,-specific R-Smads (AR-Smads) or BMP-specific R-Smads (BR-Smads). R-Smads form complexes with Co-Smads and translocate into the nucleus, where they regulate the transcription of target genes. AR-Smads bind to various proteins, including transcription factors and transcriptional co-activators or co-repressors, whereas BR-Smads interact with other proteins less efficiently than AR-Smads. Id proteins are induced by BR-Smads, and play important roles in exhibiting some biological effects of BMPs. Understanding the mechanisms of TGF-, superfamily signalling is thus important for the development of new ways to treat various clinical diseases in which TGF-, superfamily signalling is involved. [source] MIDA1 is a sequence specific DNA binding protein with novel DNA binding propertiesGENES TO CELLS, Issue 9 2000Toshiaki Inoue Background Id proteins not only regulate cell differentiation negatively, but they also promote growth and apoptosis. To know the mechanism of how Id regulates cell fate, we previously isolated an Id-associating protein, MIDA1, which positively regulates cell growth. Its predicted amino acid sequence contains tryptophan-mediated repeats (Tryp-med repeats) similar to the DNA binding region of the c-Myb oncoprotein. We determined whether MIDA1 can bind to DNA in a sequence specific manner by PCR-assisted binding site selection. Results We identified a 7-base sequence (GTCAAGC) surrounded by a 1,3 bp palindromic sequence as the DNA sequence recognized by the Tryp-med repeats of MIDA1. This motif is located within the 5,-flanking sequence of several growth regulating genes. Gel shift assays revealed that this sequence and a certain length of flanking DNA are necessary for MIDA1 to bind DNA in a stable manner. Methylation interference and DNase I footprint analysis suggested that the DNA binding of MIDA1 is resistant to DNA methylation and that MIDA1 does not specifically localize on this particular motif. Conclusions We concluded that MIDA1 is a novel sequence-specific DNA binding protein with some different properties from the usual transcription factors and that MIDA1 may act as a mediator of Id-mediated growth-promoting function through its DNA binding activity. [source] In Vivo Function of a Differentiation Inhibitor, Id2IUBMB LIFE, Issue 4 2001Yoshifumi Yokota Abstract Cell differentiation is an essential process for the development of various cell types that constitute multicellular organisms. During development, the large family of factors bearing a helix-loop-helix (HLH) motif participates profoundly in this process and these factors serve as good experimental tools for investigating mechanisms underlying tissue-specific differentiation. The HLH family includes both positive and negative regulators of cell differentiation: basic HLH (bHLH)-type transcription factors and Id proteins, respectively. Following an exciting decade focusing on bHLH factors, advances achieved in studies of the inhibitory factors in the last couple of years have placed them in the front line of the research on differentiation and proliferation control. Here, we present and discuss recent results obtained using Id2 -deficient mice, which manifest intriguing phenotypes in various systems. [source] Induction of Id2 expression by cardiac transcription factors GATA4 and Nkx2.5JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2008Joong-Yeon Lim Abstract Inhibitor of differentiation/DNA binding (Id) proteins function as a regulator of helix-loop-helix proteins participating in cell lineage commitment and differentiation. Here, we observed a marked induction of Id2 during cardiomyocyte differentiation from P19CL6 murine embryonic teratocarcinoma stem cells, prompting us to investigate the upstream regulatory mechanism of Id2 induction. Computer analysis of Id2 promoter and subsequent electrophoretic mobility shift assay revealed several binding sites for GATA4 and Nkx2.5 within the Id2 promoter. By further deletion and mutation analysis of the respective binding site, we identified that two motifs located at ,497/,502 and ,264/,270 were functionally important for Id2 promoter activation by GATA4 and Nkx2.5, respectively. Overexpression of GATA4 and/or Nkx2.5 induced not only Id2 promoter activity but also Id2 protein expression. Additionally, Id proteins significantly inhibit the GATA4 and Nkx2.5-dependent transcription, suggesting Id proteins may play a regulatory role in cardiogenesis. Collectively, our results demonstrate that GATA4 and Nkx2.5 could be one of the upstream regulators of Id2. J. Cell. Biochem. 103: 182,194, 2008. © 2007 Wiley-Liss, Inc. [source] Non-redundant inhibitor of differentiation (Id) gene expression and function in human prostate epithelial cellsTHE PROSTATE, Issue 9 2006Ananthi J. Asirvatham Abstract BACKGROUND The four Id (inhibitor of differentiation) proteins (Id1, Id2, Id3, and Id4) dimerize and neutralize the transcriptional activity of basic helix-loop-helix (bHLH) proteins. The Id proteins negatively regulate differentiation and promote proliferation hence the expression of specific subsets of Id proteins is high in many different types of cancers. However, the expression of all the Id isoforms and their potential function in specific cancer cell types is not known. In this study, the expression and function of all four Id isoforms in prostate cancer cell lines was investigated to gain a better understanding of the role of each Id isoform in normal prostate epithelial and prostate cancer cells. METHODS Id gene and protein expression was evaluated in the context of androgen response. The cellular function of Id isoforms was evaluated by targeted loss of function of Id genes. RESULTS The four Id isoforms are differentially expressed and regulated in normal human prostate epithelial cells versus prostate cancer cell lines DU145 and LNCaP. Id4 is present only in AR positive cells (normal and LNCaP) and its expression regulated by androgens. Loss of Id1 and Id3 expression by siRNA results in loss of proliferation. Loss of Id2 had no effect on proliferation but increased apoptosis. CONCLUSIONS A complex equilibrium between Id isoforms determines the cell fate. Id1 and Id3 target cellular proliferation, Id2 targets apoptosis, and Id4 may act as a potential tumor suppressor in prostate epithelial cells. Prostate 66: 921,935, 2006. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||