Disease relevance of Spic

• SsaM and SpiC interact and regulate secretion of Salmonella pathogenicity island 2 type III secretion system effectors and translocators [1].

High impact information on Spic

• We propose that the wild-type strain, through the action of SPI-2 effectors (including SpiC), diverts the Salmonella-containing vacuole from the endocytic pathway, and subsequent recruitment and maintenance of vacuolar ATPase/lgp-containing membranes that enclose replicating bacteria is mediated by translocation of SifA [2].
• Here, we establish that the SPI-2-encoded SpiC protein is exported by the Spi/Ssa type III secretion system into the host cell cytosol where it interferes with intracellular trafficking [3].
• Two of these genes are orthologs of mammalian PU.1 and Spi-C, respectively, whereas the third gene, Spi-D, is a different family member [4].
• Among changed genes, matrix metalloproteinase (MMP)-12, apoptosis inhibitor 6 (Api-6), erythroblast transformation-specific domain (Ets) transcription factor family member Spi-C, and oncogene MafB were increased 100-, 70-, 40-, and 10-fold, respectively, in lal-/- lungs versus the wild-type lungs [5].
• Spi-C RNA was expressed in mature B lymphocytes and at lower levels in macrophages [6].

Biological context of Spic

• In the attempt to isolate the novel Ets family protein, we have screened cDNA libraries with the yeast one-hybrid method and identified a new PU.1-related factor, Prf [7].
• Spi-C was encoded by a single-copy gene that was mapped to chromosome 10, region C. Spi-C interacted with DNA similarly to PU.1 as judged by methylation interference, band-shift and site selection analysis, and activated transcription of a kappaY element reporter gene upon co-transfection of HeLa cells [6].
• Together, these results show that SpiC is involved in the process of SPI-2 secretion and indicate that phenotypes associated with a spiC- mutant are caused by the inability of this strain to translocate effector proteins, thus calling for further investigation into the function(s) of this protein [8].
• An antibody against SpiC detected the protein on immunoblots from total cell lysates of S. typhimurium expressing SpiC from a plasmid, but it was not detected in secreted fractions after exposure of cells to conditions that result in secretion of other SPI-2 effector proteins [8].

Anatomical context of Spic

• Possible roles of Prf with respect to the B cell differentiation are discussed [7].
• Furthermore, pre-B cell and plasma cell lines were Spi-C-negative, suggesting that Spi-C might be a regulatory molecule during a specific phase of B lymphoid development [6].
• By inactivating Hook3 function, the SpiC protein may alter the lysosome network and prevent phagosome-lysosome fusion [9].

Physical interactions of Spic

• The novel Ets protein was most closely related to PU.1 and Spi-B within the DNA binding Ets domain and was therefore named Spi-C [6].

Other interactions of Spic

• Prf, a novel Ets family protein that binds to the PU.1 binding motif, is specifically expressed in restricted stages of B cell development [7].

Analytical, diagnostic and therapeutic context of Spic

• Fractionation assays and immunofluorescence microscopy were used to investigate the localization of SsaM and SpiC in macrophages [1].

References