Reactome | Release of SEPT4 from mitochondria

Release of SEPT4 from mitochondria

Stable Identifier

R-HSA-6805811

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol, mitochondrial outer membrane

ReviewStatus

5/5

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Septin 4 gene (SEPT4) encodes several protein isoforms including SEPT4_i2 (also known as apoptosis-related protein in the TGF-beta signaling pathway (ARTS)) (Larisch S et al. 2000).

ARTS (SEPT4_i2) is a mitochondrial pro-apoptotic tumor suppressor protein (Larisch S et al. 2000; Elhasid et al. 2004; Gottfried Y et al. 2004; Lotan R et al. 2005). Following induction of apoptosis, ARTS rapidly translocates to the cytosol where it binds and inhibits X-linked inhibitor of apoptosis protein (XIAP). ARTS is thought to induce apoptosis by promoting the proteasome-mediated degradation of XIAP and blocking its ability to inhibit caspases (Gottfried Y et al. 2004; Bornstein B et al. 2011; Garrison JB et al. 2011; Reingewertz TH et al. 2011). The release of ARTS from mitochondria and its accumulation in the cytosol appears to be a caspase-independent event (Gottfried Y et al. 2004). The protein level of ARTS is tightly regulated through ubiquitin mediated degradation (Lotan R et al. 2005). The translocation of ARTS (SEPT4) from mitochondria precedes the release of both cytochrome c (CYCS) and SMAC (DIABLO) and leads to degradation of XIAP before the release of SMAC (Edison N et al. 2012).

Literature References

PubMed ID	Title	Journal	Year
15029247	The mitochondrial ARTS protein promotes apoptosis through targeting XIAP Steller, H, Lotan, R, Gottfried, Y, Larisch, S, Rotem, A	EMBO J.	2004
11146656	A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif Yi, Y, Larisch, S, Lotan, R, Tony Parks, W, de Caestecker, MP, Steller, H, Duckett, CS, Orly, J, Lechleider, RJ, Kerner, H, Danielpour, D, Gottfried, Y, Kim, SJ, Book-Melamed, N, Birkey Reffey, S, Timberg, R, Eimerl, S, Roberts, AB	Nat. Cell Biol.	2000