Tsz-Leung To and Narendra Maheshri at MIT describe positive-feedback loops in gene regulatory networks which may exhibit bimodal responses in Science this week. Using a synthetic system in budding yeast, To and Maheshri show that “a promoter with multiple transcription factor binding sites can induce a steady-state bimodal response without cooperative binding of the TF.” The researcher’s deterministic models did not predict bistability, however, which is a finding contrary to common thought.
A trio of researchers report their finding that inhibition of the NF-κB signaling by A20, a zinc finger protein, occurs through the disruption of ubiquitin conjugating enzyme complexes. They show that A20 inhibits the E3 ligase activities of three genes ― TRAF6, TRAF2, and cIAP1 ― by antagonizing interactions with the enzymes Ubc13 and UbcH5c. “A20, together with the regulatory molecule TAX1BP1, interacted with Ubc13 and UbcH5c and triggered their ubiquitination and proteasome-dependent degradation,” the team writes. They suggest that their findings suggest the role of A20 in the inhibition of inflammatory signaling pathways.
Also in Science this week, German researchers report that two insecticidal toxins in the bacterium Photorhabdus luminescens force actin polymerization. They found that the concerted action of both toxins inhibited phagocytosis of target cells and induced extensive intracellular clustering of actin.
In a perspectives article in Science Translational Medicine this week, Ludmila Prokunina-Olsson and Stephen Chanock at the National Cancer Institute report their review of the Leary et al. PARE method for massive, parallel, and near-complete sequencing of individual tumor genomes. In “Cancer gets a little more personal,” the authors write that the researchers findings support that notion that cancer genomes contain myriad genetic alterations, many of which are unique to individual tumors. Prokunina-Olsson and Chanock also write that further validation, and a reduction of cost, in the PARE method is required.