In Cell this week, researchers in Italy say that TAZ, a transducer of the Hippo pathway, is responsible for conferring the properties of cancer stem cells onto breast cancer cells. TAZ is required to sustain self-renewal and tumor-initiation capacities in breast cancer stem cells, the authors write. "TAZ protein levels and activity are elevated in prospective CSCs and in poorly differentiated human tumors and have prognostic value," they add. This suggests that cancer stem cells are linked to the Hippo pathway in breast cancer.
Also in Cell this week, researchers in California write that ribosome profiling of mouse embryonic stem cells shows how complex and dynamic mammalian proteomes are. The team presents a suite of techniques that can be used to construct genome-wide maps of protein synthesis. "We exploit the propensity of harringtonine to cause ribosomes to accumulate at sites of translation initiation together with a machine learning algorithm to define protein products systematically," the authors write. "Analysis of translation in mouse embryonic stem cells reveals thousands of strong pause sites and unannotated translation products. These include amino-terminal extensions and truncations and upstream open reading frames with regulatory potential, initiated at both AUG and non-AUG codons, whose translation changes after differentiation."
Researchers at the Albert Einstein College of Medicine in New York report a network of broadly expressed HLH genes which regulates tissue-specific cell fates in Cell this week. "In Drosophila, a cross-interacting regulatory network links expression of the E protein Daughterless (Da), which heterodimerizes with bHLH proteins to activate them, with expression of the Id protein Extramacrochaetae (Emc), which antagonizes bHLH proteins," the team writes. "Coupled transcriptional feedback loops maintain the widespread Emc expression that restrains Da expression, opposing bHLH-dependent differentiation while enhancing growth and cell survival." A similar regulatory mechanism is found in many Drosophila tissues, they add, as well as in mammalian cells.
And finally in Cell this week, a group of researchers reports that gene activation programs are mediated by non-coding RNA- and Pc2 methylation-dependent gene relocation. Growth signals can cause a response of methylation or demethylation of Pc2, which in turn controls the relocation of growth-control genes between Polycomb bodies and interchromatin granules, the team reports. "This movement is the consequence of binding of methylated and unmethylated Pc2 to the ncRNAs TUG1 and MALAT1/NEAT2, located in PcGs and ICGs, respectively," the authors write. "These ncRNAs mediate assembly of multiple corepressors/coactivators and can serve to switch mark recognition by readers of the histone code. Additionally, binding of NEAT2 to unmethylated Pc2 promotes E2F1 SUMOylation, leading to activation of the growth-control gene program."