Integration of autography, proteasomal degradation, unfolded protein responce and apoptosis

A single cell has the potential to kill an entire human being. Efforts to cure cancer are limited by survival of individual cancer cells despite immune surveillance and toxic therapies. Understanding the intricate network of pathways that maintain cellular homeostasis and mediate stress response or default into cell death is critical to the development of strategies to eradicate cancer. Autophagy, proteasomal degradation and the unfolded protein response (UPR) are cellular pathways that degrade and recycle excess or damaged proteins to maintain cellular homeostasis and survival. This review will discuss autophagy and how it is integrated with proteasomal degradation and UPR to govern cell fate through restoration of cellular homeostasis or default into the apoptotic cell death pathway. The first response of autophagy is macroautophagy, which sequesters cytoplasm including organelles inside double-membraned autophagosome vesicles that fuse with lysosomes to degrade and recycle the contents. Ubiquitination patterns on proteins targeted for degradation determine whether adapter proteins will bring them to developing autophagosomes or to proteasomes. Macroautophagy is followed by chaperone-mediated autophagy (CMA), in which Hsc70 (Heat shock cognate 70) selectively binds proteins with exposed KFERQ motifs and pushes them inside lysosomes through the LAMP-2A (Lysosome-associated membrane protein type 2A) receptor. These two processes and the lesser understood microautophagy, which involves direct engulfment of proteins into lysosomes, occur at basal and induced levels. Insufficient proteasome function or ER stress induction of UPR can induce autophagy, which can mitigate damage and stress. If this network is incapable of repairing the damage or overcoming continued stress, the default pathway of apoptosis is engaged to destroy the cell. Induction of macroautophagy by cancer therapeutics has led to clinical trials investigating combinations of HCQ (hydroxychloriquine) suppression of autophagy with apoptosis-inducing agents. Further study of the complex integration of autophagy, proteasomal degradation, UPR and apoptosis is likely to provide additional targets for our fight against cancer. This article is part of a Special Issue entitled “Apoptosis: Four Decades Later”

The 1985-1986 South Pole balloon campaign

This paper will provide an overview of the University of Houston-University Park/University of Maryland-College Park balloon program that was carried out at Amundsen-Scott Station, South Pole, Antarctica, during the 1985-1986 austral summer. The paper will emphasize objectives, instrumentation and operations. The quality of the data and periods of special interest will be discussed while final conclusions will be left necessarily to a later time. The primary experimental tools used in this program were unmanned stratospheric balloon payloads. The balloons used were helium-filled and had a volume of 5100m^3. The payloads had a mass of 24.5kg, giving a nominal float altitude of 32km. The payloads were instrumented with three-axis, doubleprobe field detectors and X-ray scintillation counters. Secondary instrumentation onboard measured the stratospheric conductivity, the ambient temperature and pressure. Three of the payloads also included tone-ranging transceivers. Equally essential to the program are the ground-based data from the South Pole Station Cusp Lab, the newly developed conjugate observatory, the Goose Bay HF radar, the Sφndrestrφm radar, and satellite data from the DE spacecraft. In the month starting on 16 December 1985 and ending 16 January 1986,8 successful balloon flights were conducted, ranging in duration from 6 to 103h 30min. A total of 468h 30min of data were obtained under a wide range of magnetic conditions. Periods of particular interest include 19 December 1985,28 December 1985,30 December 1985,2-3 January 1986,and 7-8 January 1986