Endogenously expressed truncated P2X7 receptor lacking the C-terminus is preferentially upregulated in epithelial cancer cells and fails to mediate ligand-induced pore formation and apoptosis.
A truncated naturally occurring variant of the human purinergic receptor P2X7 (P2X7-R) was found in human cancer cervical cells. The novel protein consists of 258 amino acids, and compared to the wild-type P2X7-R it lacks the entire intracellular carboxy terminus, the second transmembrane domain, and the distal third of the extracellular loop. The truncated P2X7-R failed to form pores and mediate apoptosis, and it interacted with the wild-type P2X7-R in a manner suggesting auto-hetero-oligomerization. In contrast to cancer cells the novel truncated P2X7-R was expressed relatively little in normal cervical cells. These data raise the possibility that coexpression of the truncated form could block P2X7 mediated apoptosis and promote uncontrolled growth of cells.
Feng
Y H
YH
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Li
X
X
Zeng
R
R
Gorodeski
G I
GI
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis* / Q000737:chemistry; D058486:Receptors, Purinergic P2X7; D012878:Skin Neoplasms / Q000378:metabolism*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism
C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7