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