Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.5.1.2 (DNA ligase)
 2,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1beta-converting enzyme (ICE)/Ced-3 proteases play a critical role in apoptosis. One well characterized substrate of these proteases is the DNA repair enzyme poly(ADP-ribose) polymerase. We report here that alpha-fodrin, an abundant membrane-associated cytoskeletal protein, is cleaved rapidly and specifically during Fas- and tumor necrosis factor-induced apoptosis; this cleavage is mediated by an ICE/Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease. Studies in cells treated with these apoptotic stimuli reveal that both fodrin and poly(ADP-ribose) polymerase proteolysis are inhibited by acetyl-Tyr-Val-Ala-Asp chloromethyl ketone and CrmA, specific inhibitors of ICE/Ced-3 proteases. However, fodrin proteolysis can be distinguished from poly(ADP-ribose) polymerase proteolysis by its relative insensitivity to acetyl-Asp-Glu-Val-Asp aldehyde (DEVD-CHO), a selective inhibitor of a subset of ICE/Ced-3 proteases that includes CPP32. DEVD-CHO protects cells from Fas-induced apoptosis but does not prevent fodrin proteolysis, indicating that cleavage of this protein can be uncoupled from apoptotic cell death. Moreover, purified fodrin is cleaved in vitro by CPP32 (but not by ICE) into fragments of the same size observed in vivo during apoptosis. These findings suggest that fodrin proteolysis in vivo may reflect the activity of multiple ICE/Ced-3 proteases whose partial sensitivity to DEVD-CHO reflects a limited contribution from CPP32, or an ICE/Ced-3 protease less sensitive than CPP32 to DEVD-CHO inhibition.
 ...
PMID:Specific cleavage of alpha-fodrin during Fas- and tumor necrosis factor-induced apoptosis is mediated by an interleukin-1beta-converting enzyme/Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease. 894 Jan 32

The transcription regulatory function of p53 was analyzed by using two inducible p53 systems in the human lung cancer cell line H1299. cDNA probes derived from RNA harvested 12 h after p53 induction were used to probe filters containing cDNA arrays. Over 20 genes were found to be significantly induced or suppressed by p53. The induced genes can be classified mainly as cell cycle inhibitors like p21waf, GADD45, apoptosis-related genes like Fas/APO1 and PIG3 or DNA repair genes like DDB2, DNA ligase and G/T mismatch DNA glycosylase. The suppressed genes include mainly cell cycle regulators like cyclin B1, cyclin H and kinases like c-abl, CLK1 and others. The most notable induced gene was MIC-1, encoding a TGF-beta-related secretory protein, suggesting a potential paracrine component for p53 growth suppression.
 ...
PMID:Profile of gene expression regulated by induced p53: connection to the TGF-beta family. 1072 49

Cell-mediated cytotoxic responses are critical for control of Marek's disease virus (MDV) infection and tumour development. However, the mechanisms of virus clearance mediated by cytotoxic responses in the bursa of Fabricius of chickens during MDV infection are not fully understood. In this study, the host cytotoxic responses during MDV infection in the bursa were investigated by examining the expression of genes in the cell lysis pathways. Partial up-regulation existed in the expression of the important cytolytic molecule granzyme A (GzmA), Fas, NK lysin and DNA repair enzyme Ape1, whereas little or no expression appeared in other cytolytic molecules, including perforin (PFN) and Fas ligand (FasL), and molecules involved in DNA repair and apoptosis in the bursa during MDV infection. These results suggest that less sustained cytotoxic activities are generated in the bursa of MDV-infected chickens. The findings of this study provide a more detailed insight into the host cytotoxic responses to MDV infection.
 ...
PMID:Characterization of cytotoxicity-related gene expression in response to virulent Marek's disease virus infection in the bursa of Fabricius. 2316 36