Apoptosis regulatory protein Siva (SIVA1)

Apoptosis regulatory protein Siva (SIVA1) is a proapoptotic intracellular protein encoded by the SIVA1 gene, which plays an important regulatory role in caspase-dependent programmed cell death (apoptosis), cell cycle progression, and cell proliferation[2][3][5][6]. It is directly involved in mediating CD27-induced apoptosis by binding the cytoplasmic tail of the CD27 antigen, part of the tumor necrosis factor receptor (TNFR) superfamily[2][3][6]. SIVA1 inhibits the antiapoptotic actions of BCL2L1 (Bcl-x(L)), disrupts NF-kappa-B signaling, and facilitates T cell receptor-mediated apoptosis[6]. It also mediates the ubiquitination of proliferating cell nuclear antigen (PCNA) after DNA damage, implicating a broader role in maintaining genomic integrity[3][5]. In neurons, SIVA1 modulates synaptic plasticity by regulating the interplay between FAIM-L and XIAP, promoting caspase-3 activation and AMPA receptor internalization, linking it to synaptic and neurodegenerative disorders such as Alzheimer’s disease[1]. Two Siva isoforms (Siva-1 and Siva-2) arise from alternative splicing[2]. SIVA1 interacts with multiple proteins central to apoptosis and cell survival, but it is not currently a direct drug target or clinical biomarker[6][3].

Other names

SIVASiva-1Siva-2CD27-binding proteinCD27BPApoptosis inducing factor SivaApoptosis regulatory protein Siva-1

Not applicable (no drug directly targeting SIVA1 documented as of search) — SIVA1 itself induces apoptosis via disruption of antiapoptotic protein interactions (e.g., BCL2L1/Bcl-x(L), XIAP) and acts as an E3 ubiquitin ligase — it modulates apoptosis by protein-protein interactions and regulatory ubiquitination[3][6][1].