11 research outputs found
Establishment and characterisation of a human carcinoma cell line with acquired resistance to Aplidinâ„¢
DNA profiling of tumor buds in colorectal cancer indicates that they have the same mutation profile as the tumor from which they derive
Impact of Reducing DNA Input on Next-Generation Sequencing Library Complexity and Variant Detection
Resistance to targeted therapies as a multifactorial, gradual adaptation to inhibitor specific selective pressures
Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics
Calcineurin Activates Cytoglobin Transcription in Hypoxic Myocytes*
Cardiac hypertrophy develops in response to a variety of cardiovascular
stresses and results in activation of numerous signaling cascades and
proteins. In the present study, we demonstrate that cytoglobin is a
stress-responsive hemoprotein in the hypoxia-induced hypertrophic myocardium
and it is transcriptionally regulated by calcineurin-dependent transcription
factors. The cytoglobin transcript level is abundantly expressed in the adult
heart and in response to hypoxia cytoglobin expression is markedly
up-regulated within the hypoxia-induced hypertrophic heart. To define the
molecular mechanism resulting in the induction of cytoglobin, we undertook a
transcriptional analysis of the 5′ upstream regulatory region of the
cytoglobin gene. Evolutionarily conserved binding elements for transcription
factors HIF-1, AP-1, and NFAT are located within the upstream region of the
cytoglobin gene. Transcriptional assays demonstrated that calcineurin activity
modulates cytoglobin transcription. Increased calcineurin activity enhances
the ability of NFAT and AP-1 to bind to the putative cytoglobin promoter,
especially under hypoxic conditions. In addition, inhibition of calcineurin,
NFAT, and/or AP-1 activities decreases endogenous cytoglobin transcript and
protein levels. Thus, the regulation of cytoglobin transcription by
calcineurin-dependent transcription factors suggests that cytoglobin may have
a functional role in calcium-dependent events accompanying cardiac
remodeling