sptssb is a small subunit of the SPT holoenzyme, which typically comprises two large subunits (SPTLC1/2) and a small subunit (sptssa or sptssb). In Xenopus tropicalis, the recombinant sptssb protein has the following characteristics:
The protein stimulates SPT activity by altering substrate affinity and specificity, influencing the chain length of sphingolipid long-chain bases (LCBs) .
sptssb modulates SPT activity by interacting with large subunits to regulate substrate binding. Key findings include:
In Xenopus tropicalis and other models, sptssb mutations (e.g., Stellar in mice) increase SPT’s affinity for C18 fatty acyl-CoA substrates, elevating C20 LCB production . This gain-of-function effect is critical for studying sphingolipid homeostasis.
Parameter | Wild-Type SPT | Mutant SPT (Stellar) | Source |
---|---|---|---|
Kₘ (C18 substrate) | Higher | 50% lower (higher affinity) | |
Vₘₐₓ | Basal activity | Slightly increased |
The recombinant sptssb is used in:
C20 LCB Production: Mutations in sptssb elevate C20 sphingosine and ceramides, linked to neurodegeneration and protein misfolding in mice .
Cancer Research: SPTSSB upregulation in prostate cancer (PCa) cells after anti-androgen therapy suggests its role in de novo sphingolipid synthesis and therapeutic resistance .
sptssb-expressing Xenopus cell lines (e.g., XTN-6, XTN-8) enable studies of sphingolipid pathways in developmental biology and disease modeling .
The Stellar mutation in mice increases C20 LCBs, causing axon degeneration and ubiquitinated protein accumulation .
Elevated C20 ceramides disrupt membrane integrity and protein homeostasis .
SPTSSB knockdown reduces de novo sphingolipid synthesis in AR-negative prostate cancer cells, enhancing therapeutic efficacy .