scholarly journals The influence of 2- chlorodeoxyadenosine in combination with tumour necrosis factor-α or its mutein on murine leukaemias L1210 and P388

1995 ◽  
Vol 4 (3) ◽  
pp. 205-208 ◽  
Author(s):  
J. Góra-Tybor ◽  
K. Warzocha ◽  
T. Robak
Keyword(s):  
Biological Activity ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Survival Times ◽  
Terminal Amino Acid ◽  
N Terminus ◽  
Terminal Amino ◽  
Factor Α ◽  
Necrosis Factor

We investigated the influence of 2-chlorodeoxyadenosine (2-CdA) in combination with tumour necrosis factor-α (TNFα) or its mutein VI, which differs from the native molecule by N-terminal amino acid composition, on the survival time of mice inoculated with leukaemia L1210 or P388. Groups of mice with leukaemia L1210 and P388 receiving 2-CdA combined with TNFα had shorter survival times than animals treated with these agents separately. In contrast, the administration of 2-CdA in conjunction with mutein VI, prolonged the survival of mice inoculated with these leukaemias as compared with animals receiving these agents separately. The results of the present study emphasize the importance of the biological activity of the TNFα molecule N-terminus.

scholarly journals Functional analysis of tumour necrosis factor-α-related apoptosis-inducing ligand (TRAIL): cysteine-230 plays a critical role in the homotrimerization and biological activity of this novel tumoricidal cytokine

2000 ◽  
Vol 350 (2) ◽  
pp. 505-510 ◽  
Author(s):  
Danyah TRABZUNI ◽  
Konrad S. FAMULSKI ◽  
Manzoor AHMAD
Keyword(s):  
Functional Analysis ◽  
Biological Activity ◽  
Chemical Modification ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Critical Role ◽  
Tumour Necrosis Factor Α ◽  
Apoptotic Activity ◽  
Factor Α ◽  
Necrosis Factor

We have determined that the mutation of the cysteine-230 residue to either glycine or serine in TRAIL (tumour necrosis factor-α-related apoptosis-inducing ligand) results in the formation of a structurally incompetent dimer and a consequent loss of apoptotic activity. Similarly, chemical modification of the thiol residues present in both reduced and Zn2+-depleted trimer converts TRAIL into an inactive dimer. We postulate that cysteine-230 plays a critical role in homotrimerization of this tumoricidal cytokine.

Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

2003 ◽  
Vol 70 ◽  
pp. 39-52 ◽  
Author(s):  
Roy A. Black ◽  
John R. Doedens ◽  
Rajeev Mahimkar ◽  
Richard Johnson ◽  
Lin Guo ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Recent Work ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Transforming Growth Factor ◽  
Intrinsic Activity ◽  
Converting Enzyme ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

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