"In search for interaction partners that might serve as regulators or targets of this kinase we identified apoptosis antagonizing transcription factor (AATF), a nuclear phosphoprotein of 523 amino acids."

"AATF contains an extremely acidic domain and a putative leucine zipper characteristic of transcription factors. Indeed, a Gal4-BD-AATF fusion protein exhibited strong transactivation activity."

"Interestingly, AATF interfered with Dlk-induced apoptosis."

"Here we describe Che-1, a novel human protein that interacts with hRPB11. Che-1 possesses a domain of high homology with Escherichia coli RNA polymerase final sigma-factor 70 and SV40 large T antigen."

"Che-1 interacts with the retinoblastoma susceptibility gene (Rb) by two distinct domains. Functionally, we demonstrate that Che-1 represses the growth suppression function of Rb, counteracting the inhibitory action of Rb on the trans-activation function of E2F1."

"These results identify a novel protein that binds Rb and the core of pol II, and suggest that Che-1 may be part of transcription regulatory complex."

"we have carried out a proteomic analysis to draw up a list of proteins present within nucleoli of HeLa cells. This analysis allowed the identification of 213 different nucleolar proteins."

"Functional classification of these proteins allowed outlining several biological processes taking place within nucleoli. Notably, a role in ribosome biogenesis was proposed for 31 proteins."

"Che-1 activates p21WAF1/Cip1 by displacing histone deacetylase (HDAC)1 from the Sp1 binding sites of the p21WAF1/Cip1 gene promoter and accumulating acetylated histone H3 on these sites."

"Che-1-specific RNA interference negatively affects p21WAF1/Cip1 transactivation and increases cell proliferation in HCT116 cells. Taken together, our results indicate that Che-1 can be considered a general HDAC1 competitor."

"We previously demonstrated that Che-1 inhibits the Rb growth-suppressing function by interfering with Rb-mediated HDAC1 recruitment on E2F target gene promoters."

"AATF colocalizes with Par-4 in both cytoplasmic and nuclear compartments, and it interacts directly and selectively with Par-4 via the leucine zipper domain in neural cells."

"Co-expression of AATF completely blocked aberrant production and secretion of Abeta-(1-42) induced by Par-4, and AATF/Par-4 complex formation was essential for the inhibitory effect of AATF on aberrant Abeta secretion."

"These results indicate that AATF is an endogenous antagonist of Par-4 activity and an effective inhibitor of aberrant Abeta production and secretion under apoptotic conditions."

"AATF (apoptosis-antagonizing transcription factor), a leucine zipper protein initially identified as an interaction partner of DAP like kinase (Dlk), is expressed in cortical neurons and in neural PC12 cells. Abeta induces alterations in AATF expression in cortical neurons. Inhibition of AATF induction sensitizes neurons to Abeta toxicity."

"Overexpression of AATF suppressed superoxide production, inhibited peroxynitrite formation and membrane lipid peroxidation, and protected against Abeta-induced apoptosis in PC12 cells. These results suggest that AATF is a novel neuroprotective factor and it may protect against Abeta-induced apoptosis through its effects on suppressing the production of reactive oxygen species (ROS)."

"Che-1 contributes to DNA damage response and its depletion sensitizes cells to anticancer agents. The checkpoint kinases ATM/ATR and Chk2 interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage."

"These Che-1 modifications induce a specific recruitment of Che-1 on the TP53 and p21 promoters. Interestingly, it has a profound effect on the basal expression of p53, which is preserved following DNA damage."

"Notably, Che-1 contributes to the maintenance of the G2/M checkpoint induced by DNA damage. These findings identify a mechanism by which checkpoint kinases regulate responses to DNA damage."

"We show that AATF is induced by ER stress through the PERK-eIF2alpha pathway and transcriptionally activates the v-akt murine thymoma viral oncogene homolog 1 (AKT1) gene through signal transducer and activator of transcription 3 (Stat3), which sustains Akt1 activation and promotes cell survival."

"Ectopic expression of AATF or a constitutively active form of AKT1 confers on cells resistance to ER stress-mediated cell death, whereas RNAi-mediated knockdown of AATF or AKT1 renders cells sensitive to ER stress."

"We also discovered a positive crosstalk between the AATF and WFS1 signaling pathways. Thus, WFS1 deficiency or AATF deficiency mediates a self-perpetuating cycle of cell death."

"Upon genotoxic stress, AATF is phosphorylated by the checkpoint kinase MK2. Phosphorylation results in the release of AATF from cytoplasmic MRLC3 and subsequent nuclear translocation."

"where AATF binds to the PUMA, BAX and BAK promoter regions to repress p53-driven expression of these pro-apoptotic genes."

"In xenograft experiments, mice exhibit a dramatically enhanced response of AATF-depleted tumours following genotoxic chemotherapy with adriamycin. The exogenous expression of a phospho-mimicking AATF point mutant results in marked adriamycin resistance in vivo. These data identify the p38/MK2/AATF signalling module as a critical repressor of p53-driven apoptosis."

"Co-immunoprecipitation and co-localization experiments were used to demonstrate association of AATF both with two ADA2 isoforms, ADA2A and ADA2B and with GCN5 proteins in human cells and yeast two-hybrid assays to delineate domains in the ADA2 and GCN5 proteins required for these interactions."

"ADA2B produced the strongest interaction with AATF, while ADA2A and GCN5 displayed weaker, nonetheless definite interaction. ADA2B co-localization with AATF was primarily in the nucleoplasm with an additional nucleolar co-localization. Unlike AATF, GCN5 appeared to be excluded from the nucleolus."

"For hGCN5, amino or carboxy-terminal truncations that removed the acetyltransferase domain no longer manifested interaction with AATF suggesting this domain is required for the association. For both ADA2 isoforms, the region between the SANT domain and the Ada1 box also may be critical for interaction with AATF while the SWIRM domain is not required."

"AATF expression activates the promoter while co-expression of ADA2A, ADA2B or GCN5 with AATF, significantly reduced the activation imparted by AATF on MDM2 promoter-directed transcription (p <0.01)."

"AATF was mostly found in the nucleoplasm. Like ADA2B, the AATF protein, was also localized in the nucleolus in addition to the nucleoplasm. Che-1/AATF could be participating in the regulation of gene expression by regulating chromatin structure."

"We report the high-resolution cryo-electron microscopy structures of maturing human small subunit (SSU) processomes at resolutions of 2.7 to 3.9 angstroms."

"The human small subunit processome mediates early maturation of the small ribosomal subunit by coupling RNA folding to subsequent RNA cleavage and processing steps. RNA folding states within these particles are communicated to and coordinated with key enzymes that drive irreversible steps such as targeted exosome-mediated RNA degradation, protein-guided site-specific endonucleolytic RNA cleavage, and tightly controlled RNA unwinding."

"These conserved mechanisms highlight the SSU processome's impressive structural plasticity, which endows this 4.5-megadalton nucleolar assembly with the distinctive ability to mature the small ribosomal subunit from within."