P160 steroid coactivator

The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA . These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The mediator of RNA polymerase II transcription subunit 1 protein is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID , is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes [., thyroid hormone receptor -(TR-) associated proteins that interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors]. It also regulates p53 -dependent apoptosis and it is essential for adipogenesis . This protein is known to have the ability to self-oligomerize. [7]

DDT and its metabolites activate the HIF-1 response element (HRE) . The VEGFA gene contains an estrogen responsive element ( Kazi et al. 2005 ; Stoner et al. 2000 , 2004 ) and is regulated by estrogens in mammary and uterine cells ( Hyder et al. 1996 ; Nakamura et al. 1996 , 1999 ). However, VEGFA expression is down-regulated by E 2 in human breast cancer cells ( Hyder et al. 1998 ). We previously showed that DDT stimulated transcription in ERα-negative human embryonic kidney cells by activating the HRE ( Bratton et al. 2009 ). Because VEGFA contains an HRE within its promoter ( Liu et al. 1995 ), we tested the effects of DDT and DDT metabolites on transcription of an HRE-luc reporter construct in MCF-7 breast cancer cells. Transcription was more than doubled in response to 10 μM o,p ´-DDT ( Figure 2A ). HRE activity also increased significantly in response to the active metabolites p,p ´-DDT, p,p ´-DDD, o,p ´-DDE, and p,p ´-DDE, but not in response to the inactive metabolite p,p ´-DDA ( Figure 2A ). E 2 also activated the HRE-luc reporter in MCF-7 cells, but this effect was blocked by ICI ( Figure 2B ). This suggests that E 2 can activate HREs; this is not surprising considering the general nature of the HRE reporter and the possibility that HREs are located within genes mediated by ERα–E 2 . Our cumulative results suggest that DDT alters VEGFA expression in MCF-7 cells in part by activating an HRE within the VEGFA promoter, in a manner independent of the ERα or E 2 . However, the fact that E 2 stimulates an HRE reporter in MCF-7 cells leaves open the possibility that the DDT effect on VEGFA expression could be mediated, at least in part, through the ERα-E 2 pathway.

P160 steroid coactivator

p160 steroid coactivator


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