Proteolysis regulation

Figure 4. Ubiquitin-mediated proteolysis regulates the onset and demise of Cdk activity during the cell division cycle. The Anaphase Promoting Complex/Cyclosome (APC/C) is active from the onset of anaphase until the end of G1 phase, during which it targets mitotic cyclins (Clbs) and other proteins such as Pdsl. The SCF complex is constitutively active but only targets Sicl and other substrates once they have been specifically phosphorylated by G1 cyclin (Cln)-Cdk (Cdc28) activity. See text for details.

Werb Z (1997) ECM and cell surface proteolysis regulating cellular ecology. Cell 91(4) 439—442... 

Synthesis of thyroid hormones has several stages. In the thyroid gland, iodine ions are oxidised to the active form (cation 1+) by the action of a specific thyroid peroxidase (thyroperoxidase), which reacts with tyrosyl residues of thyroglobulin to form 3-iodotyrosine. Subsequent iodisation of 3-iodotyrosine yields 3,5-diiodotyrosine. The condensation reaction of 3,5-diiodotyrosine with 3-iodotyrosine in the colloid of the thyroid follicle yields 3,5,3 -triiodothyronine. Two molecules of 3,5-diiodotyrosine combine to form thyroxine. These hormones, bound to thyroglobulin, are then released into the blood as a result of thyroglobulin proteolysis regulated by thyrotropin. In the blood, normal concentrations of 3,5,3 -triiodothyronine can vary by as much as 1-1.5 p,g/l, and thyroxine concentrations range from 60 to 120 (xg/l. 

INSULIN. Some protein hormones are synthesized in the form of inactive precursor molecules, from which the active hormone is derived by proteolysis. For instance, insulin, an important metabolic regulator, is generated by proteolytic excision of a specific peptide from proinsulin (Figure 15.3). 

APP undergoes proteolytic processing by several secretases. First, the bulk of the ectodomain needs to be removed by membrane-bound a- or (3-secretases leading to secreted forms of APP and membrane-bound C-terminal fragments a-CTF or (3-CTF, respectively. Regulated intramembrane proteolysis (RIP) of the (3-CTF by y-secretase occurs only after ectodomain shedding and releases the A(3 pqrtide from the membrane (Fig. 2). 

Disorders caused by misfolded mutant proteins that fail to pass the quality control system of the ER (e.g., mutations of the cystic fibrosis transmembrane regulator protein (CFTR) causing cystic fibrosis). The mutant proteins are retrotranslocated into the cytosol and finally subjected to proteolysis. In some... 

Regulation of Anti-HIV Properties of Chemokines by Limited Proteolysis... 

Fig. 2.2 Simplified scheme of oxidant/antioxidant regulation ofNF-KB activation. Different stimuli, leading to an increase of ROS generation inside the ceU, activate the phosphorylation of IkB inhibitory protein and the subsequent proteolysis. Thioredoxin (Trx) may reduce activated NF-kB proteins facilitating nuclear translocation.Qnce released from IkB, the NF-kB complex translocates into the nucleus and the binding to DNA domain in the promoters and enhancers of genes such as TNF-a, IL-1, proliferation and chemotactic factors, adhesion molecule. Some of these genes, in turn, may further induce NF-kB activation, leading to a vicious circle if the regulatory cellular system escapes from...

N7. Niedbala, M. J., Cytokine regulation of endothelial cell extracellular proteolysis. Agents Actions Suppl. 42, 179-193 (1993). 

Brown MS, Goldstein JL. The SREBP pathway regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 1997 89 331-340. 

Regulation of neuropeptide expression is exerted at several levels. Control of neuropeptide function is mediated by factors controlling rates of prepropeptide gene transcription, translation, peptide degradation and secretion (Fig. 18-11). On the scale of seconds to minutes, peptide secretion is not always coupled lock-step with classical transmitter release (example above). Peptides are inactivated by diffusion and by proteolysis, so it would be expected that inhibition of specific extracellular proteases... 

Selkoe, D. and Kopan, R. Notch and presenilin regulated intramembrane proteolysis links development and degeneration. Annu. Rev. Neurosci. 26 565-597,2003. 

Thyroid hormone is liberated into the bloodstream by the process of proteolysis within thyroid cells. T4 and T3 are transported in the bloodstream by three proteins thyroid-binding globulin, thyroid-binding prealbumin, and albumin. Only the unbound (free) thyroid hormone is able to diffuse into the cell, elicit a biologic effect, and regulate thyroid-stimulating hormone (TSH) secretion from the pituitary. 

Saksela, O., Plasminogen activation and regulation of pericellular proteolysis. Biochim. Biophys. Acta 823, 35-65 (1985). 

---