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Transcriptional Complex (transcriptional + complex)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

The basic helix-loop-helix factor Hand2 regulates autonomic nervous system development

DEVELOPMENTAL DYNAMICS, Issue 3 2005
Yuka Morikawa
Abstract Mammalian autonomic nervous system (ANS) development requires the combinatorial action of a number of transcription factors, which include Mash1, Phox2b, and GATA3. Here we show that the bHLH transcription factor, Hand2 (dHAND), is expressed concurrently with Mash1 during sympathetic nervous system (SNS) development and that the expression of Hand2 is not dependent on Mash1. This suggests that these two bHLH factors work in parallel during SNS development. We also show that ectopic expression of Hand2 activates the neuronal program and promotes the acquisition of a phenotype corresponding to peripheral neurons including neurons of the SNS lineage in P19 embryonic carcinoma cells. We propose that Hand2 works in parallel with other members of the transcriptional network to regulate ANS developmental but can ectopically activate the program by a cross-regulatory mechanism that includes the activation of Mash1. We show that this function is dependent on its interaction with the histone acetyltransferase p300/CBP, indicating that Hand2 functions to promote ANS development as part of a larger transcriptional complex. Developmental Dynamics 234:613,621, 2005. © 2005 Wiley-Liss, Inc. [source]

Chromosome band 16q22-linked familial AML: Exclusion of candidate genes, and possible disease risk modification by NQO1 polymorphisms

GENES, CHROMOSOMES AND CANCER, Issue 3 2004
Robert Escher
Analyses of chromosomal translocation and inversion breakpoints in sporadic acute myeloid leukemias have identified many transcription factors as playing a role in leukemogenesis. Studies of families with a Mendelian predisposition to hematological malignancies have identified the gene coding for the transcription factor RUNX1 as a leukemia-predisposing gene involved in the first steps of leukemogenesis. Using two families, another autosomal dominant familial leukemia locus was linked to chromosome band 16q22 where the CBFB gene maps. Although CBFB forms a core-binding factor transcriptional complex with RUNX1, previous analyses have excluded the CBFB gene as the leukemia-predisposing gene in these families. In the current study, we performed an extended molecular analysis in these families of the four other transcription factor genes in the 16q22 critical region as well as of two other genes with a known association with leukemia. Several previously undescribed but nonpathogenic sequence variants were identified. We demonstrated that the transcription factors E2F4, CTCF, NFATC3, and NFAT5, and the genes coding for NAD(P)H:quinone oxido-reductase 1 (NQO1) and for E-cadherin are not responsible for the leukemia susceptibility in these families. The presence of NQO1 polymorphisms may suggest a role for this gene in disease risk modification in these families. © 2004 Wiley-Liss, Inc. [source]

Differently regulated androgen receptor transcriptional complex in prostate cancer compared with normal prostate

INTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2005
MASASHIGE KINOSHITA
Abstract Background:, The coregulators of androgen receptors (AR) influence the transcriptional activity of AR. In order to better understand the mechanism of carcinogenesis in the prostate, we investigated the relationship between AR and AR coregulators in the early stage of prostate cancer. Methods:, mRNA was purified from 15 samples of prostate cancer and normal tissue and transcribed into cDNA. We screened eight AR coregulators for different gene expressions in prostate cancer, comparing these with normal tissue by a real-time polymerase chain reaction Syber green method, then quantified each component of the AR transcriptional complex by a real-time PCR hybri-probe method. The extent of gene expression similarity was compared by simple Pearson correlation coefficient analysis between prostate cancer and normal tissue. We applied a z-test to calculate significant differences between r-values. Results:, We found that the gene expression level of FHL2 decreased in prostate cancer compared with that of normal tissue and the gene expressions of PSA, AR and SMRT were not significant. The correlation coefficient analysis revealed that strong associations were found in the pairs of AR versus SMRT, AR versus FHL2 and SMRT versus FHL2 in prostate cancer, whereas similarity was found only in the pair of AR versus FHL2 in normal tissue. No association was observed between prostate-specific antigen and other genes. Conclusion:, These results demonstrate that the AR-AR coregulator relationship is different between prostate cancer and normal tissue, leading to the hypothesis that the AR transcriptional complex is regulated differently between prostate cancer and normal tissue. [source]

Wnt signaling inside the nucleus

CANCER SCIENCE, Issue 4 2008
Miki Shitashige
Accumulation of the ,-catenin protein and transactivation of a certain set of T-cell factor (TCF)-4 target genes by accumulated ,-catenin have been considered crucial in colorectal carcinogenesis. In the present review, we summarize nuclear proteins that interact with, and regulate, the ,-catenin and TCF and lymphoid enhancer factor (LEF) transcriptional complexes. Our recent series of proteomic studies has also revealed that various classes of nuclear proteins participate in the ,-catenin,TCF-4 complex and modulate its transcriptional activity. Furthermore, the protein composition of the TCF-4-containing nuclear complex is not fixed, but is regulated dynamically by endogenous programs associated with intestinal epithelial cell differentiation and exogenous stimuli. Restoration of the loss-of-function mutation of the adenomatous polyposis coli (APC) gene in colorectal cancer cells does not seem to be a realistic approach with currently available medical technologies, and only signaling molecules downstream of the APC gene product can be considered as targets of pharmacological intervention. Nuclear proteins associated with the ,-catenin,TCF-4 complex may include feasible targets for molecular therapy against colorectal cancer. Recently, an inhibitor of the interaction between CREB-binding protein and ,-catenin was shown to efficiently shut down the transcriptional activity of TCF-4 and induce apoptosis of colorectal cancer cells. We also summarize current strategies in the development of drugs against Wnt signaling. (Cancer Sci 2008; 99: 631,637) [source]