Scotin, a novel p53-inducible proapoptotic protein located in the ER and the nuclear membrane

Abstract

p53 is a transcription factor that induces growth arrest or apoptosis in response to cellular stress. To identify new p53-inducible proapoptotic genes, we compared, by differential display, the expression of genes in spleen or thymus of normal and p53 nullizygote mice after γ-irradiation of whole animals. We report the identification and characterization of human and mouse Scotin homologues, a novel gene directly transactivated by p53. The Scotin protein is localized to the ER and the nuclear membrane. Scotin can induce apoptosis in a caspase-dependent manner. Inhibition of endogenous Scotin expression increases resistance to p53-dependent apoptosis induced by DNA damage, suggesting that Scotin plays a role in p53-dependent apoptosis. The discovery of Scotin brings to light a role of the ER in p53-dependent apoptosis.

Caspase-12: an overview

“…[15][16][17] Caspase-12 has been localized on the cytoplasmic side of the ER using immunofluorescence and subcellular fractionation techniques. 10,11,13 ER stress can be induced by chemicals such as brefeldin A, tunicamycin, thapsigargin and the calcium ionophore A23187.…”

“…Caspase-8-cleaved Bap31 plays a role during Fas-mediated cell death. 15,17 Scotin and NRADD are two additional ER-residing proapoptotic molecules that have recently been discovered. 12,17 Scotin has been implicated in p53-mediated apoptosis.…”

“…15,17 Scotin and NRADD are two additional ER-residing proapoptotic molecules that have recently been discovered. 12,17 Scotin has been implicated in p53-mediated apoptosis. 17 In ST14A cells, CrmA and the vFLIP proteins E8 and MC159 inhibit NRADD-induced apoptosis.…”

“…12,17 Scotin has been implicated in p53-mediated apoptosis. 17 In ST14A cells, CrmA and the vFLIP proteins E8 and MC159 inhibit NRADD-induced apoptosis. Interestingly, a dominant-negative form of NRADD exerts significant protection against ER-stress-inducing agents (thapsigargin, Catalytic subunit (CSU) (c) phylogenetic analysis of the catalytic part of the human and murine caspases.…”

Apoptosis and disease: a matter of cell fate

“…In addition, TAp73 induces ER stress mediated by the direct transactivation of Scotin, 7 a p53-inducible gene cloned by David Lane's group. 8 So how does DNp73 perform its survival function? The DNp73 isoform, by tetramerisation with TAp73 or p53, was shown to reduce the transcription of Bax and Puma and inhibit apoptosis.…”