The cyclin-dependent kinase PITSLRE/CDK11 is required for successful autophagy

(Macro)autophagy is a membrane-trafficking process that serves to sequester cellular constituents in organelles termed autophagosomes, which target their degradation in the lysosome. Autophagy operates at basal levels in all cells where it serves as a homeostatic mechanism to maintain cellular integrity. The levels and cargoes of autophagy can, however, change in response to a variety of stimuli, and perturbations in autophagy are known to be involved in the aetiology of various human diseases. Autophagy must therefore be tightly controlled. We report here that the Drosophila cyclin-dependent kinase PITSLRE is a modulator of autophagy. Loss of the human PITSLRE orthologue, CDK11, initially appears to induce autophagy, but at later time points CDK11 is critically required for autophagic flux and cargo digestion. Since PITSLRE/CDK11 regulates autophagy in both Drosophila and human cells, this kinase represents a novel phylogenetically conserved component of the autophagy machinery

Bromodomain protein BRD4 is a transcriptional repressor of autophagy and lysosomal function

Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations. In the case of starvation, a signaling cascade involving AMPK and histone deacetylase SIRT1 displaces chromatin-bound BRD4, instigating autophagy gene activation and cell survival. Importantly, this program is directed independently and also reciprocally to the growth-promoting properties of BRD4 and is potently repressed by BRD4-NUT, a driver of NUT midline carcinoma. These findings therefore identify a distinct and selective mechanism of autophagy regulation

The Effect of Conductive Alginate Capsules Encapsulating Rejuvenator (HealRoad Capsules) on the Healing Properties of 10 mm Stone Mastic Asphalt Mix

Conductive alginate capsules encapsulating a bitumen rejuvenator (HealRoad capsules) has demonstrated good healing abilities in pure bitumen and mortar mixes. HealRoad capsules can efficiently heal damage via induction heating. They also release the encapsulated rejuvenator, thereby rejuvenating aged bitumen. These findings indicate that HealRoad capsules and induction heating systems combined could represent a possible asphalt pavement maintenance method. This paper investigated the effect of HealRoad capsules on the mechanical performance of the 10 mm stone mastic asphalt mix and measured the damage repair (healing) efficiency of the capsules in an asphalt mix. The results indicate that in small amounts, >1%, HealRoad capsules do not degrade the mix performance (indirect tensile strength and rutting resistance) and in some cases, the HealRoad capsules actually improve mix performance, e.g., in terms of the indirect tensile strength ratio (water sensitivity). However, the HealRoad capsules are unable to stimulate induction healing due to the small volume of capsules within the mix. Further investigation demonstrated that increasing the capsules in the mix to >5% can stimulate induction heating effectively. However, it also indicated that a high content of HealRoad capsules reduces the asphalt mix strength. The study has shown that HealRoad capsules are an effective healing system for high bitumen content mixtures such as mortar mixtures but is an inefficient healing system for a full asphalt mix, such as the 10 mm stone mastic asphalt mixMaterials and Environmen

Loss of autophagy affects melanoma development in a manner dependent on PTEN status

No abstract available