Functional analysis of tumour necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL): cysteine-230 plays a critical role in the homotrimerization and biological activity of this novel tumoricidal cytokine.
We have determined that the mutation of the cysteine-230 residue to either glycine or serine in TRAIL (tumour necrosis factor-alpha-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 Zn(2+)-depleted trimer converts TRAIL into an inactive dimer. We postulate that cysteine-230 plays a critical role in homotrimerization of this tumoricidal cytokine.
Trabzuni
D
D
Laboratory of Molecular Apoptosis and Cancer Therapy, Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, MBC-03 Riyadh 11211, Saudi Arabia.
Famulski
K S
KS
Ahmad
M
M
D051017:Apoptosis Regulatory Proteins; D002845:Chromatography; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology; D003545:Cysteine / Q000737:chemistry*; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015032:Zinc / Q000737:chemistry
D051017:Apoptosis Regulatory Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D005982:Glutathione Transferase; D015032:Zinc; D003545:Cysteine