The action of androgens in regulating development and growth is mediated by androgen receptor (AR). AR is a member of the steroid hormone receptor superfamily, a class of receptors that function through their ability to regulate the transcription of specific genes. The AR is located in various target tissues, with its levels and activity altered with the onset of various cellular events (e.g., sexual development, malignant transformation). The modulation of AR levels occurs through a number of mechanisms, including transcription, and is regulated by various factors (e.g., androgens). The ability of AR to modulate gene transcription is through its interaction with specific DNA sequences located near or within the target gene promoter. The importance of the AR in reproductive physiology has been emphasized by the finding of AR mutations, leading to a variety of disorders, including testicular feminization syndrome. In this article, we review the structure and function of AR and the role AR plays in the function of the mammalian system.
RNA polymerase II is a multisubunit enzyme involved in the transcription of protein encoding genes. Recently acquired knowledge of the transcription process and of the RNA polymerase molecule as well as the isolation of subunit clones have led to a better understanding of the enzyme's functional regulation. Specific transcription initiation occurs at promoter regions located upstream of the gene and requires a minimum of five basic factors in addition to the enzyme. Furthermore, proteins that bind to specific DNA elements within the promoter also regulate transcriptional activity. Additional factors are required for the elongation and, possibly, termination of transcription. Two elongation factors, SII and TFIIF, interact directly with the RNA polymerase II molecule. Functional domains of RNA polymerase II have been determined by analysis of genomic clones for the two largest subunits of the enzyme. For example, the 240-kDa largest subunit contains a highly phosphorylated carboxyl-terminal heptapeptide domain repeated 26-52 times that is absolutely required for transcription in vivo. Analysis of the polymerase molecule and its interaction with basic gene-specific transcription factors will aid in our studies of the control of gene expression.
Background: Several high throughput technologies have been employed to identify differentially regulated genes that may be molecular targets for drug discovery. Here we compared the sets of differentially regulated genes discovered using two experimental approaches: a subtracted suppressive hybridization (SSH) cDNA library methodology and Affymetrix GeneChip ® technology. In this "case study" we explored the transcriptional pattern changes during the in vitro differentiation of human monocytes to myeloid dendritic cells (DC), and evaluated the potential for novel gene discovery using the SSH methodology.
hUBC9, an E2 ubiquitin conjugating enzyme, was identified by yeast two-hybrid screening and coprecipitation studies to interact with MEKK1 and the type I TNF-K K receptor, respectively. Because both of these proteins regulate NFU UB activity, the role of hUBC9 in modulating NFU UB activity was investigated. Overexpression of hUBC9 in HeLa cells stimulated the activity of NFU UB as determined by NFU UB reporter and IL-6 secretion assays. hUBC9 also synergized with MEKK1 to activate NFU UB reporter activity. Thus, hUBC9 modulates NFU UB activity which, at least in part, can be attributed to its interaction with MEKK1 and the type I TNF-K K receptor.z 1998 Federation of European Biochemical Societies.
Because chronic pain patients "move" in and out of employment and for work capacity status after pain facility treatment, future outcome studies using these measures will have to consider carefully the impact of "movement" on their results.
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