XIAP

Cilia effects upon perturbation of XIAP

Cilia number / % ciliated:

Decreased cilia number

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Mouse phenotype:

increased igg1 level, absent testes

Subcellular localization

cilia associated gene

Functional category

• Ciliary assembly/disassembly
• Protein processing & maturation
• Signaling (Hedgehog, GPCRs, ion channels)

Function

Profibrotic stimuli disrupt primary cilia on quiescent hepatic stellate cells (HSCs) by inducing XIAP-mediated ubiquitination and proteasomal degradation of IFT88. This contributes to HSC activation and liver fibrosis. Primary cilia exist on multiple cell types in the liver, but only cilia present on HSCs disassemble during liver fibrosis. TGF-β enhances XIAP-mediated ubiquitination of IFT88, promoting its proteasomal degradation. Blocking XIAP-mediated IFT88 degradation ablates TGF-β-induced HSC activation(PMID: 38351372).