Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor suppressor gene product p53 in its wild-type conformation, is an effector of apoptosis. A rat histiocytic tumor, AK-5 which has a rearranged and mutated p53 gene undergoes apoptosis upon heat shock through surface expression of CD95 receptor. DNA sequence analysis of p53 gene from tumor cells revealed a deletion of 'C' at nucleotide position 942 and an addition of 'A' at position 1055. Deletion of one nucleotide caused premature termination of p53 protein which resulted in shorter p53 protein with an altered sequence from amino acids 315 to 341. Altered p53 was unable to protect BC-8, a single cell clone of AK-5 cells from apoptosis upon heat shock. BC-8 cells transfected with a wild-type p53gene (3B4 cells) were resistant to heat induced apoptosis and did not show the expression CD95 death receptor. Inhibition of p53 expression by using antisense oligo induced apoptosis upon heat shock in 3B4 cells. Similarly, inhibition of CD95 expression by antisense oligo inhibited heat induced apoptosis in BC-8 cells. In addition, cell cycle regulatory molecules, cdc2 and cdk2 are differentially regulated in a non-cell cycle dependent manner in these tumor cells. These results, in view of lack of heat shock response in BC-8 cells suggest a complex interaction between p53, CD95 and hsp70 which determines the fate of the cell. In the absence of functional p53, CD95 appears to be an effector of apoptosis in BC-8 cells.
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PMID:Effect of C-terminal deletion of P53 on heat induced CD95 expression and apoptosis in a rat histiocytoma. 1203 86

The aim of this study was to identify key genes whose expression is altered by heme and heme deficiency in the human erythroleukemia K562 cells and in the NGF-induced rat pheochromocytoma neuronal PC12 cells, respectively. By quantitative RT-PCR, Northern blotting, and Western blotting analyses, we found that the expression of the CDK inhibitors p18 and p21 was upregulated at the early and late stages of heme-induced erythroid differentiation of K562 cells, respectively, while the expression of cyclin D1 was downregulated. Data from succinyl acetone and desferrioxamine treatments suggest that these effects of heme in K562 cells were specific. Further, by microarray expression analysis, we found that inhibition of heme synthesis by succinyl acetone in NGF-induced PC12 cells drastically altered the expression of several groups of important neuronal genes, including the structural genes encoding neurofilament proteins and synaptic vesicle proteins, regulatory genes encoding signaling components beta-arrestin and p38 MAPK, and stress-response genes encoding hsp70. These results show that heme and heme deficiency affect the expression of diverse genes in a cell-type specific manner in mammalian cells, and that heme, although needed at different levels, is critical for both erythropoiesis and neurogenesis. These studies provide insights into how heme may act to control diverse regulatory processes in mammals.
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PMID:An examination of heme action in gene expression: heme and heme deficiency affect the expression of diverse genes in erythroid k562 and neuronal PC12 cells. 1204 72

NF-Y transcription factor binds to CCAAT boxes on promoters of cell cycle regulatory genes such as cdc2, cyclin B, cdc25C, and cyclin A. We previously reported that the DNA binding activity of NF-Y is regulated by p53-p21-cdk2 pathway. CBF/HSP70 was originally identified as a transcription factor binding to the CCAAT box on the hsp70 promoter and mediates transcription repression of hsp70 pro- moter by p53. Recently it was demonstrated that CBF/HSP70 interacts and cooperates with NF-Y. In this study, we found that p53 represses the trans-cription of CBF/HSP70. Since transactivation ability of NF-Y is regulated in a cell cycle-dependent manner, we examined the transcription of CBF/HSP70 during the cell cycle. After synchronization of a human bladder carcinoma cell lacking functional p53 at early S phase, we infect the cells with adenovirus encoding p53. Cells infected with control virus progressed to S and G2 after release from the arrest. In contrast, cells expressing p53 enter S and G2 phases, but arrest at G2/M. The expression of CBF/HSP70 was induced at S/G2 phase in cells infected with a control virus, but kept to be repressed in cells expressing p53. Thus, these results suggest that p53 suppresses the expression of cell cycle regulatory genes though inhibiting both CCAAT binding factors, CBF/HSP70 and NF-Y.
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PMID:Transcription repression of a CCAAT-binding transcription factor CBF/HSP70 by p53. 1626 74