Coordinated Induction of the Ubiquitin Conjugation Pathway Accompanies the Developmentally Programmed Death of Insect Skeletal Muscle

Abstract

The developmentally programmed cell death of abdominal intersegmental muscles in the tobacco hawk-moth Manduca sexta is coincident with a 10-fold induction of the polyubiquitin gene as a hormonally regulated event (Schwartz, L. M., Myer, A., Kosz, L., Engelstein, M., and Maier, C. (1990) Neuron 5, 411-419). Solid phase immunochemical assays measuring intersegmental muscle pools of free and conjugated ubiquitin reveal that the induction of polyubiquitin mRNA is accompanied by a proportional increase in total ubiquitin polypeptide. Ubiquitin conjugate pools increase 10-fold at eclosion, during which loss of muscle protein mass is maximum. A smaller but measurable increase in ubiquitin conjugates is observed earlier in pupal development coincident with a modest enhanced degradation of myofibrillar proteins. Accumulation of ubiquitin conjugates is accompanied by induction in the pathway for polypeptide ligation, including the activating enzyme (E1), several carrier protein (E2) isoforms, and ubiquitin:protein isopeptide ligase (E3). Both accumulation of ubiquitin polypeptide and the enzymes of the conjugation pathway are subject to regulation by declining titers of the insect molting hormone 20-hydroxyecdysone, which signals onset of programmed cell death in the intersegmental muscles. Thus, programmed cell death within the intersegmental muscles is accomplished in part by stimulation of the ubiquitin-mediated degradative pathway through a coordinated induction of ubiquitin and the enzymes responsible for its conjugation to yield proteolytic intermediates. This suggests enzymes required for ubiquitin conjugation may represent additional genes recruited for developmentally programmed death.

Global Gene Expression Profiles During Acute Pathogen-Induced Pulmonary Inflammation Reveal Divergent Roles for Th1 and Th2 Responses in Tissue Repair

“…Furthermore, mice deficient in IL-10, resulting in enhanced Th1 responses, succumbed to infection with an avirulent strain of Toxoplasma gondii, with markedly enhanced liver and lung necrosis (29,30). Numerous studies have also implicated ubiquitin in the proteolysis that accompanies apoptosis (31)(32)(33)(34). Although no gross necrosis was observed in the lung sections during this limited time period, the apparent activation of the cell cycle could be the organism's attempt to compensate for cells lost due to tissue damage.…”

Ubiquitin‐protein conjugates selectively distribute during early chicken embryogenesis

“…Emerging evidence suggests a role for the ubiquitin system in selective developmental processes (Pickart et al, 1989;Schwartz et al, 1990;Glotzer et al, 1991;Scotting et al, 1991;Muralidhar and Thomas, 1993;Haas et al, 1995). We have therefore taken the first systematic approach towards identifying and characterizing ubiquitin and its associated enzymes in early development using a single vertebrate animal model.…”

“…Studies have demonstrated a role for ubiquitin in the degeneration of the intersegmental muscles (ISM) following pupation in the tobacco hawkmoth, Manduca sexta (Schwartz et al, 1990). Subsequently, it was revealed that a 10-fold increase in ISM ubiquitin-conjugate levels, under the regulation of glucocorticoid 20-hydroxyecdysone, is responsible for the ISM developmentally programmed cell death (Haas et al, 1995). Scotting et al (1991) described a limited study using chicken embryos in which ubiquitinated proteins were immunohistochemically detected in the cells of the lens, notochord, and myotome.…”

Programmed cell death during plant growth and development

“…Hence proteolytic pathways involving both thiol proteases and perhaps ubiquitin conjugation appear to be active just before degeneration of specific cell types in anthers, suggesting a role for multiple proteolytic systems during anther cell death. The ubiquitin-dependent pathway of proteolysis is induced during pcd in degenerating insect muscles (Haas et al, 1995).…”