18 research outputs found
Regulation of constitutive and inducible AHR signaling : complex interactions involving the AHR repressorstar
Author Posting. © Elsevier B.V., 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Biochemical Pharmacology 77(2009): 485-497, doi:10.1016/j.bcp.2008.09.016.The AHR is well known for regulating responses to an array of environmental chemicals.
A growing body of evidence supports the hypothesis that the AHR also plays perhaps an even
more important role in modulating critical aspects of cell function including cell growth, death,
and migration. As these and other important AHR activities continue to be elucidated, it becomes
apparent that attention now must be directed towards the mechanisms through which the AHR
itself is regulated. Here, we review what is known of and what biological outcomes have been
attributed to the AHR repressor (AHRR), an evolutionarily conserved bHLH-PAS protein that
inhibits both xenobiotic-induced and constitutively active AHR transcriptional activity in
multiple species. We discuss the structure and evolution of the AHRR and the dominant
paradigm of a xenobiotic-inducible negative feedback loop comprised of AHR-mediated
transcriptional up-regulation of AHRR and the subsequent AHRR-mediated suppression of AHR
activity. We highlight the role of the AHRR in limiting AHR activity in the absence of
xenobiotic AHR ligands and the important contribution of constitutively repressive AHRR to
cancer biology. In this context, we also suggest a new hypothesis proposing that, under some
circumstances, constitutively active AHR may repress AHRR transcription, resulting in unbridled
AHR activity. We also review the predominant hypotheses on the molecular mechanisms
through which AHRR inhibits AHR as well as novel mechanisms through which the AHRR may
exert AHR-independent effects. Collectively, this discussion emphasizes the importance of this
understudied bHLH-PAS protein in tissue development, normal cell biology, xenobiotic
responsiveness, and AHR-regulated malignancy.Supported by P01-ES11624 (D.H.S.), ArtBeCAUSE (D.H.S.), R01ES006272 (M.E.H.),
P42ES007381 (M.E.H. and D.H.S.
Effects of hydrogen-rich saline on early acute kidney injury in severely burned rats by suppressing oxidative stress induced apoptosis and inflammation
Effects of audio coaching and visual feedback on the stability of respiration during radiotherapy
The Drosophila melanogaster condensin subunit Cap-G interacts with the centromere-specific histone H3 variant CID
Specificity of Vascular Reactivity and Remodeling After Repeated Endothelial Injury in a Swine Model
CENP-C Is Involved in Chromosome Segregation, Mitotic Checkpoint Function, and Kinetochore Assembly
CENP-C is a conserved inner kinetochore component. To understand the precise roles of CENP-C in the kinetochore, we created a cell line with a conditional knockout of CENP-C with the tetracycline-inducible system in which the target protein is inactivated at the level of transcription. We found that CENP-C inactivation causes mitotic delay. However, observations of living cells showed that CENP-C-knockout cells progressed to the next cell cycle without normal cell division after mitotic delay. Interphase cells with two nuclei before subsequent cell death were sometimes observed. We also found that ∼60% of CENP-C–deficient cells had no Mad2 signals even after treatment with nocodazole, suggesting that lack of CENP-C impairs the Mad2 spindle checkpoint pathway. We also observed significant reductions in the signal intensities of Mis12 complex proteins at centromeres in CENP-C–deficient cells. CENP-C signals were also weak in interphase nuclei but not in mitotic chromosomes of cells with a knockout of CENP-K, a member of CENP-H complex proteins. These results suggest that centromere localization of CENP-C in interphase nuclei occurs upstream of localization of the Mis12 complex and downstream of localization of the CENP-H complex