Alternative titles; symbols
HGNC Approved Gene Symbol: PSRC1
Cytogenetic location: 1p13.3 Genomic coordinates (GRCh38): 1:109,279,556-109,283,145 (from NCBI)
PSRC1 is a microtubule-interacting and -bundling protein that appears to have a prosurvival function (Hsieh et al., 2008).
By searching an EST database for sequences similar to mouse Dda3, followed by PCR and screening of a fetal brain cDNA library, Lo and Wang (2002) cloned human PSRC1, which they called DDA3. The deduced 333-amino acid protein shares 68.2% identity with mouse Dda3, with highest conservation in the N-terminal half. Both mouse and human DDA3 are rich in serine and proline and contain a coiled-coil domain, and 3 of 6 PxxP motifs in mouse Dda3 are conserved in human DDA3. PCR analysis revealed variable DDA3 expression in all human tissues examined except skeletal muscle. Highest expression was detected in fetal thymus and adult brain.
Using immunofluorescence analysis of HeLa cells, Hsieh et al. (2008) showed that DDA3 exhibited a cytoplasmic filamentous-like pattern of localization and colocalized with tubulin (see 602259).
Hsieh et al. (2002) identified a potential intronic p53 (TP53; 191170) response element in the mouse Dda3 gene. Mobility shift and reporter gene assays confirmed that p53 bound this element and induced Dda3 expression. Dda3 was induced by DNA damage in mouse embryonic fibroblasts in a p53-dependent manner. In addition, p73 (TP73; 601990) used the p53 response element to induce Dda3 expression.
Hsieh et al. (2008) found that, in contrast to the effect of p53 on expression of mouse Dda3, p53 downregulated expression of human DDA3 mRNA and protein. Furthermore, expression of human DDA3 was suppressed following DNA damage. Human DDA3 lacks the intronic p53 response element found in mouse Dda3, but it has 3 putative p53 response elements in its 5-prime regulatory region. Chromatin immunoprecipitation and reporter gene assays showed that p53 bound the 5-prime region of DDA3 and suppressed DDA3 transcription. Overexpression of DDA3 in HeLa cells resulted in the formation of thick microtubule bundles around the nucleus, and this bundling activity increased in a DDA3 dose-dependent manner. DDA3 also increased the tolerance of cells toward serum withdrawal and permitted cell growth in the absence of serum.
Lo and Wang (2002) determined that the PSRC1 gene contains 8 exons and spans 7.7 kb. Hsieh et al. (2008) identified 3 p53 response elements in the 5-prime promoter region.
By genomic sequence analysis, Lo and Wang (2002) mapped the PSRC1 gene to chromosome 1p13.1. They mapped the mouse Psrc1 gene to a region of chromosome 3 that shares homology of synteny with human chromosome 1p13.1.
Hsieh, S.-C., Lo, P.-K., Wang, F.-F. Mouse DDA3 gene is a direct transcriptional target of p53 and p73. Oncogene 21: 3050-3057, 2002. [PubMed: 12082536] [Full Text: https://doi.org/10.1038/sj.onc.1205417]
Hsieh, W.-J., Hsieh, S.-C., Chen, C.-C., Wang, F.-F. Human DDA3 is an oncoprotein down-regulated by p53 and DNA damage. Biochem. Biophys. Res. Commun. 369: 567-572, 2008. [PubMed: 18291097] [Full Text: https://doi.org/10.1016/j.bbrc.2008.02.047]
Lo, P.-K., Wang, F.-F. Cloning and characterization of human and mouse DDA3 genes. Biochim. Biophys. Acta 1579: 214-218, 2002. [PubMed: 12427559] [Full Text: https://doi.org/10.1016/s0167-4781(02)00512-2]