Overall, the present results underscore that other routes, aside from the well-established CeA projections to the periaqueductal gray, may contribute to the acquisition/consolidation of the freezing response associated to a TFC task. It is suggested that CeA may presumably influence DS processing via a synaptic relay on dopaminergic neurons of the substantia nigra compacta and retrorubral
nucleus. The present observations are also in line with other studies showing that TFC and CFC responses are mediated by different anatomical networks. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The transcription BAY 1895344 in vitro factor C/EBP alpha (CEBPA) is a key player in granulopoiesis and leukemogenesis. 3-Methyladenine supplier We have previously reported the interaction of C/EBPa with other proteins ( utilizing mass spectrometry) in transcriptional regulation.
In the present study, we characterized the association of the MYST domain histone acetyltransferase Tat-interactive protein (TIP) 60 (HTA-TIP) with C/EBP alpha. We show in pull-down and co-precipitation experiments that C/EBP alpha and HTATIP interact. A chromatin immunoprecipitation (ChlP) and a confirmatory Re-ChlP assay revealed in vivo occupancy of the C/EBP alpha and GCSF-R promoter by HTATIP. Reporter gene assays showed that HTATIP is a coactivator of C/EBP alpha. The co-activator function of HTATIP is dependent on its intact histone acetyltransferase (HAT) domain and on the C/EBP alpha DNA-binding domain. The resulting balance between histone acetylation and deacetylation at the C/EBP alpha promoter might represent an important mechanism of C/EBP alpha action. We observed a lower expression of HTATIP mRNA in undifferentiated U937 cells compared ABT-737 cell line to retinoic acid-induced differentiated U937 cells, and correlated
expression of CEBPA and HTATIP mRNA levels were observed in leukemia samples. These findings point to a functional synergism between C/EBP alpha and HTATIP in myeloid differentiation and suggest that HTATIP might be an important player in leukemogenesis.”
“Raf/MEK/Erk signaling is activated in the majority of acute myeloid leukemias (AMLs), providing rationale for targeting this pathway with therapeutic intent. We investigated growth-inhibitory and proapoptotic effects of sorafenib in AML. Our studies demonstrated that sorafenib significantly inhibited the phosphorylation levels of Raf downstream target proteins MEK1/2 and Erk, induced apoptosis and inhibited colony formation in AML cell lines and in primary AML samples. Mechanistically, treatment with sorafenib resulted in upregulation of proapoptotic Bim, accompanied by an increase in Bad, Bax and Bak protein levels and decreased Mcl-1, X-linked inhibitor of apoptosis and surviving levels, which mainly led to the activation of the intrinsic apoptotic pathway.