Death signal transduction induced by co-immobilized TNF-α plus IFN-γ and the development of polymeric anti-cancer drugs.
Based on our earlier work on the apoptosis in HeLa cells induced by TNF-α plus IFN-γ, we investigate how the co-immobilized TNF-α plus IFN-γ promotes the signal transduction of HeLa cells. It is found that the free TNF-α plus IFN-γ has much stronger capability than the co-immobilized TNF-α plus IFN-γ in binding with apoptosis signaling receptors TNFR1, which allows an argument that the co-immobilized TNF-α plus IFN-γ can modulate the death pathway of HeLa cells. Subsequently, we determine the cell membrane surface receptor with which the co-immobilized TNF-α plus IFN-γ binds, and probe the expression of death receptor which induces the apoptosis pathway upstream protein FADD and TRADD. Our results reveal that the death signal transduction, induced by the co-immobilized TNF-α plus IFN-γ, is mainly realized via the IFN-γ signaling pathway rather than the TNF-α one. In addition, the transcription of STAT1 plus its Serine 727 and Tyrosine 701 phosphorylation is not the pre-requisite for inducing the cell death signal transduction. It is thus suggested that the co-immobilized TNF-α plus IFN-γ promotes the activation of some unknown key markers in response to IFN-γ, and the binding of the co-immobilized TNF-α plus IFN-γ with some other TNF-α receptors results in enhanced programmed cell death in HeLa cells.
Guan
Yan-Qing
YQ
Laboratory of Laser Life Science, School of Life Science and MOE Key, South China Normal University, Guangzhou 510613, China.
Li
Zhibin
Z
Liu
Jun-Ming
JM
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D055808:Drug Discovery; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D055767:Immobilized Proteins / Q000494:pharmacology*; D007371:Interferon-gamma / Q000737:chemistry / Q000494:pharmacology*; D018613:Microscopy, Confocal; D008954:Models, Biological; D011108:Polymers / Q000737:chemistry*; D014176:Protein Biosynthesis / Q000187:drug effects; D017471:Receptors, Interferon / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D013057:Spectrum Analysis; D013499:Surface Properties / Q000187:drug effects; D053199:TNF Receptor-Associated Death Domain Protein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D053200:Fas-Associated Death Domain Protein; D055767:Immobilized Proteins; D011108:Polymers; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D053199:TNF Receptor-Associated Death Domain Protein; D014409:Tumor Necrosis Factor-alpha; C120411:interferon receptor, type II; D007371:Interferon-gamma