Interferon (IFN)-gamma increases the sensitivity of tumor cell lines, many of which are p53 mutants, to tumor necrosis factor-alpha-mediated and anti-Fas antibody-mediated cell death. To better understand the mechanism of IFN-gamma action in modulating the cell death response independently of p53 function, we analyzed the death of the human colon adenocarcinoma cell line, HT-29, following treatment with IFN-gamma and various cytotoxic agents. Here we show that IFN-gamma modulates cell death by sensitizing the cells to killing by numerous pro-apoptotic stimuli but not pro-necrotic stimuli. Furthermore, we show that select genes from several important apoptosis-related gene families are induced by IFN-gamma, including the apoptosis-signaling receptors CD95 (Fas/APO-1) and TNFR 1 and interleukin-1beta-converting enzyme (Ice) family members Ice, CPP32 (Yama, apopain), ICErel-II (TX, Ich-2), Mch-3 (ICE-LAP3, CMH-1), Mch-4, and Mch-5 (MACH, FLICE). Of the bcl-2 family members, IFN-gamma directly induced bak but notably not bax, which is activated by p53. The IFN-responsive transcriptional activator interferon regulatory factor-1 was also strongly induced and translocated into the nucleus following IFN-gamma treatment. We propose that IFN-gamma modulates a p53-independent apoptotic pathway by both directly and indirectly inducing select apoptosis-related genes.

AHNAK is a ubiquitously expressed giant phosphoprotein that was initially identified as a gene product subject to transcriptional repression in neuroblastoma. AHNAK is predominantly nuclear in cells of nonepithelial origin, but is cytoplasmic or associated with plasma membrane in epithelial cells. In this study we show that the extranuclear localization of AHNAK in epithelial cells depends on the formation of cell–cell contacts. We show that AHNAK is a phosphorylation substrate of protein kinase B (PKB) in vitro and in vivo. Nuclear exclusion of AHNAK is mediated through a nuclear export signal (NES) in a manner that depends on the phosphorylation of serine 5535 of AHNAK by PKB, a process that also plays a major role in determining extranuclear localization of AHNAK. AHNAK is a new PKB substrate whose function, though unknown, is likely to be regulated by its localization, which is in turn regulated by PKB.

L1 has a dual function as a ribosomal protein binding rRNA and as a translational repressor binding mRNA. The crystal structure of L1 from Thermus thermophilus has been determined at 1.85 angstroms resolution. The protein is composed of two domains with the N‐ and C‐termini in domain I. The eight N‐terminal residues are very flexible, as the quality of electron density map shows. Proteolysis experiments have shown that the N‐terminal tail is accessible and important for 23S rRNA binding. Most of the conserved amino acids are situated at the interface between the two domains. They probably form the specific RNA binding site of L1. Limited non‐covalent contacts between the domains indicate an unstable domain interaction in the present conformation. Domain flexibility and RNA binding by induced fit seems plausible.

The musculoskeletal system, consisting of bones and cartilage of various types, muscles, ligaments, and tendons, is the basis of the human body. However, many pathological conditions caused by aging, lifestyle, disease, or trauma can damage its elements and lead to severe disfunction and significant worsening in the quality of life. Due to its structure and function, articular (hyaline) cartilage is the most susceptible to damage. Articular cartilage is a non-vascular tissue with constrained self-regeneration capabilities. Additionally, treatment methods, which have proven efficacy in stopping its degradation and promoting regeneration, still do not exist. Conservative treatment and physical therapy only relieve the symptoms associated with cartilage destruction, and traditional surgical interventions to repair defects or endoprosthetics are not without serious drawbacks. Thus, articular cartilage damage remains an urgent and actual problem requiring the development of new treatment approaches. The emergence of biofabrication technologies, including three-dimensional (3D) bioprinting, at the end of the 20th century, allowed reconstructive interventions to get a second wind. Three-dimensional bioprinting creates volume constraints that mimic the structure and function of natural tissue due to the combinations of biomaterials, living cells, and signal molecules to create. In our case—hyaline cartilage. Several approaches to articular cartilage biofabrication have been developed to date, including the promising technology of 3D bioprinting. This review represents the main achievements of such research direction and describes the technological processes and the necessary biomaterials, cell cultures, and signal molecules. Special attention is given to the basic materials for 3D bioprinting—hydrogels and bioinks, as well as the biopolymers underlying the indicated products.

The crystal structure of the mutant S179C of the ribosomal protein L1 from Thermus thermophilus has been determined at 1.9 Å resolution. The mutant molecule displays a small but significant opening of the cavity between the two domains. The domain movement seems to be facilitated by the flexibility of at least two conserved glycines. These glycines may be necessary for the larger conformational change needed for an induced fit mechanism upon binding RNA. The domain movement makes a disulfide bridge possible between the incorporated cysteines in two monomers of the mutant L1.