Protein distinction from degradation

To our surprise, however, we have not been able to identify free VPg in extracts of infected cells (Golini and Wimmer, unpublished results). This paradox may be explained if VPg is generated by proteolytic cleavage from a larger precursor protein only at the moment of initiation of MA synthesis, and is then covalently linked to the MA and if cleavage of VPg from newly synthesized plus strands results in the concomitant rapid degradation of the protein. A more radical hypothesis is that VPg is sjmthesized as part of a precursor protein distinct from polyprotein NCVP 00, and that this precursor protein for VPg is translated at much lower frequency than polyprotein NCVP 00 (see E. Ehrenfeld, this voliime, chapter 11). 

A development in our understanding of the possible role of protein kinases in cell cycle control stems from recent work with yeasts and other cell types [16]. The transition from G1 to S as well as from the G2 phase (which follows S) to the mitotic phase (M) appears to be controlled by the same protein kinase. The Gl/S kinase activity is associated with the accumulation of a novel family of G1 cyclins [17]. Cyclins are proteins that are synthesised and degraded at specific points in each cycle. The G1 cyclins are distinct from the cyclins required to activate the protein kinase for transition from the G2 phase to M[17]. 

Catabolism of chylomicron remnants may be viewed as the second step in the processing of chylomicrons. After the loss of apo C-II and other C and A apoproteins, LPL no longer acts upon the remnants, and they leave the capillary surface. Chylomicron remnants are rapidly removed by uptake into liver parenchymal cells via receptor-mediated endocytosis. Apo E is important in this uptake process. The chylomicron receptors in liver are distinct from the B-E receptor that mediates uptake of LDL. The hepatic receptor for chylomicrons binds with apo E, but not apo B-48. Another receptor, known as the LDL receptor-related protein (LRP), may also function in chylomicron uptake. Chylomicron remnants are transported into the lysosomal compartment where acid lipases and proteases complete their degradation. In the liver, fatty acids so released are oxidized or are reconverted to triacylglycerol, which is stored or secreted as VLDL. The cholesterol may be used in membrane synthesis, stored as cholesteryl ester, or excreted in the bile unchanged or as bile acids. 

Distinct from the lysosomal pathway are cytosolic mechanisms for degrading proteins. Chief among these mechanisms is a pathway that includes the chemical modification of a lysine side chain by the addition of ubiquitin, a 76-residue polypeptide, followed by degradation of the ubiquitin-tagged protein by a specialized proteolytic machine. Ubiquitination is a three-step process (Figure 3-13a) ... 

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