Family

Baculovirus p35, apoptosis preventing protein (IPR003429)

Short name: Baculovirus_p35

Family relationships

None.

Description

The anti-apoptotic protein p35 from baculovirus is thought to prevent the suicidal response of infected insect cells by inhibiting caspases. Ectopic expression of p35 in a number of transgenic animals or cell lines is also anti-apoptotic, giving rise to the hypothesis that the protein is a general inhibitor of caspases.

This protein belongs to MEROPS proteinase inhibitor family I50, clan IQ. Purified recombinant p35 inhibits human caspase-1, -3, -6, -7, -8, and -10 but does not significantly inhibit unrelated serine or cysteine proteases, implying that p35 is a potent caspase-specific inhibitor. The interaction of p35 with caspase-3, as a model of the inhibitory mechanism,revealed classic slow-binding inhibition, with both active-sites of the caspase-3 dimer acting equally and independently. Inhibition resulted from complex formation between the enzyme and inhibitor, which could be visualised under non-denaturing conditions, but was dissociated by SDS to give p35 cleaved at Asp87, the P1 residue of the inhibitor. Complex formation requires the substrate-binding cleft to be unoccupied [PMID: 9692966].

Infecting the insect cell line IPLB-Ld652Y with the baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV) results in global translation arrest, which correlates with the presence of the AcMNPV apoptotic suppressor, p35. However, the anti-apoptotic function of p35 in translation arrest is not solely due to caspase inactivation, but its activity enhances signalling to a separate translation arrest pathway, possibly by stimulating the late stages of the baculovirus infection cycle [PMID: 14980489].

GO terms

Biological Process

GO:0043066 negative regulation of apoptotic process

Molecular Function

GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
CATH-Gene3D
SUPERFAMILY
Pfam