Cellular survival

Guyton, K. Z. Gorospe, M. Kensler, T. W. Holbrook, N. J. Mitogen-activated protein kinase (MAPK) activation by butylated hydroxytoluene hydroperoxide implications for cellular survival and tumor promotion. Cancer Res. 1996, 56, 3480-3485. 

Brognard, J., Clark, A.S., Ni, Y., and Dennis. P.A. 2001. Akt/protein kinase b is constitutively active in nonsmall cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. 

Growth factors have been defined as proteins that stimulate cellular proliferation and promote cellular survival 471... 

Although not strictly valid, it is possible to extend this formulation to the probability of cellular survival [reproductive inactivation S(D)] by making the assumptions that (1) one lesion inactivates the cell, and (2) the number of lesions produced is Poisson-distributed. When valid (mostly for low-LET radiation), it leads to ... 

Cellular survival is crucial for any later regeneration. The survival has to be divided into two major cell types first the differentiated cells that can be replaced by their precursors like fibroblasts and epithelial cells deriving from stem cells, and those which cannot be... 

Datta SR, Brunet A, Greenberg ME. 1999. Cellular survival a play in three Akts. Genes Dev 13 2905-2927. 

There are other questions in need of answers as well. Among them, an intriguing and very fundamental question - which may be addressed through site-directed mutagenesis and controlled expression - relates to the importance of the GTPase function of G proteins. Why is pulsed activation important is it because the effector system cannot sustain continued activity or is it because the continued activity of the effector systems would be too harmful for cellular survival ... 

J. M. Boyd, G. J. Gallo, B. Elangovan, A. B. Houghton, S. Malstrom, B. J. Avery, et al. Bik, a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins. Oncogene, 11 (9), 1921-1928, 1995. 

MDTs provide a survival strategy for living organisms that are constantly assailed by a host of harmful chemicals from the environment. Because of the diversity of these xenobiotics , cellular survival mechanisms must deal with an immense variety of molecules. MDTs supply one such strategy. The patterns of abundance of drug efflux systems in different organisms do... 

Deficiencies of any of these red cell enzymes may result in impaired ATP generation and consequently loss of function of the erythrocyte. By far the majority of these disorders are hereditary in nature, although acquired deficiencies have been described, mainly in malignant disorders involving the bone marrow. Hereditary enzymatic defects in these pathways disturb the erythrocyte s integrity, shorten its cellular survival, and produce chronic nonspherocytic hemolytic anemia (CNSHA). Deficiencies of some enzymes, however, do not lead to chronic hemolytic anemia, but to acute episodes of severe hemolysis when there is increased oxidative stress on the red cell (as in some types of glucose-6-phosphate dehydrogenase deficiency). 

Pyruvate Idnase deficiency (OMIM 266200) is the most common cause of nonspherocytic hemolytic anemia due to defective glycolysis. The allelic frequency is estimated to be around 2%. The consequent lack of sufficient energy, which is required for normal functioning and cellular survival, shortens the life span of the mature PK-deficient erythrocyte. Consequently, PK-deficient patients display a phenotype of nonspherocytic hemolytic anemia albeit with variable clinical severity. The clinical symptoms vary from neonatal death to a well-compensated hemolytic anemia. Patients benefit in general from a splenectomy. Pyruvate kinase deficiency is transmitted as an autosomal recessive disease. To date, more than 130 mutations in PKLR have been reported to be associated with pyruvate kinase deficiency (see Figure 21-10 for overview see reference 221). Most (70%) of these mutations are missense mutations affecting conserved residues in structurally and functionally important domains of PK. Splice site mutations, a deletion. 

Compound 16 showed dose-dependent q totoxicity in a study of inhibition of melanin synthesis by melan-a cell hnes. The cellular survival rate was foimd to be low after treatment with 20 jtM of 16 [45]. Compound 11 inhibited melanin synthesis in the melan-a cells at a concentration of 10 p,M. The inhibition of melanin synthesis by 11 was found to be similar to that of phenylthiourea, which is a well-known melanin synthesis inhibitor [45]. The authors concluded that compound 11 is a new candidate for the development of depigmenting agents [45]. 

Methotrexate inhibits the enzyme folate reductase at two steps (Fig. 4-12). Even though the inhibition is technically a competitive one, the enzyme binds MTX much more strongly than the natural substrate, FH2 (Table 4-5). In practical terms there is no dissociation of the enzyme-drug complex. For thymidylate synthetase to continue to produce thymidylic acid (and therefore DNA), perpetual reduction of FH2 is essential for cellular survival. The efficiency of MTX inhibition of folate reductase thus indirectly becomes the mechanism by which this drug is so cytotoxic in the S phase. In addition, there is evidence that MTX may, by binding to the tetrahydrofolate coenzyme, also inhibit the thymidylate synthetase... 

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