Tumor cells protein turnover

Three examples demonstrate the importance of E3 proteins to nor-mal cell tunction. Proteins that are not broken down owing to a de-fective E3 may accumulate to create a disease of protein aggregation such as juvenile and early-onset Parkinson disease. A defect in another member of the E3 family causes Angelman syndrome, a severe neurological disorder diaracterized by mental retardation, absence of speech, uncoordinated movement, and hyperactivity. Conversely, uncontrolled protein turnover can create dangerous pathological conditions. For example, human papilloma virus (HPV) encodes a protein that activates a specific E3 enzyme. The enzyme ubiquitinates the tumor suppressor p53 and other proteins that control DNA repair, which are then destroyed. The activation of this E3 enzvme is observed in more than 90 /u of cervical carcinomas. Thus, the... 

Mgat5 l breast tumor cells removed from the mice and placed in tissue culture showed impaired focal adhesion formation in low serum conditions (Figure 3). By activating c-Sre/FAK, Shc/RAS and PI3K, the PyMT protein contributes to the reorganization of cytoskeletal structures and turnover of focal-adhesion contacts... 

Survivin, which increases in the G2/M phase of the cell cycle followed by a rapid decline in the G1 phase, is one of a number of inhibitors of apoptosis proteins. Survivin is present in most transformed cell lines and has been shown to inhibit cas-pase directly and by apoptosis (LaCasse et al. 1998). Overexpression of this protein is frequently found in many tumor cells and correlates with malignancy (Chandele et al. 2004). NO-treated tumor cells displayed a preferential loss of survivin protein expression via a proteasome-dependent pathway. Dendritic cell-mediated killing was associated with the accelerated turnover of survivin (Huang et al. 2005). In context with cell cycle-dependent responses to chemotherapy, the data in this chapter suggest the possibility that the survivin pathway can be explored to induce apoptosis in tumor cells by dendritic cells. 

Enzymatic methylation reactions of proteins and nucleic acids in presence of SAM are of fundamental for cell division, differenci-ation and the normal genome expression. SAH which is the product of SAM demethylation possesses the properties of natural inhibitor of the majority of transmethylases8,9 and apparently may exert in vivo a direct action on SAM metabolism and physioligical functions o7 cells. The high rate of tRNA turnover which is characteristic for malignant tumors is apparently due to abnormally high activity of... 

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