Alternative titles; symbols
HGNC Approved Gene Symbol: CEP72
Cytogenetic location: 5p15.33 Genomic coordinates (GRCh38): 5:612,340-676,616 (from NCBI)
Centrosomes function in microtubule organization, cilium formation, cell division, polarity, and signaling. CEP72 is a pericentriolar satellite protein that has critical roles in microtubule organization, cell division, and cilium formation (Stowe et al., 2012).
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned CEP72, which they designated KIAA1519. The deduced protein contains 648 amino acids. RT-PCR ELISA detected KIAA1519 expression in all tissues examined, with highest expression in adult testis, and lowest expression in adult skeletal muscle. Moderate KIAA1519 expression was detected in all specific adult brain regions examined.
Oshimori et al. (2009) reported that the 647-amino acid CEP72 protein contains 2 tandem leucine-rich repeats near the N terminus and a coiled-coil domain near the C terminus. Immunofluorescence analysis showed that CEP72 localized to centrosomes throughout mitosis in human cell lines.
Using immunofluorescence microscopy, Stowe et al. (2012) determined that endogenous CEP72 localized with PCM1 (600299) in pericentriolar satellites in human RPE1 cells. Western blot analysis detected CEP72 at an apparent molecular mass of 72 kD.
At the initiation of mitosis, gamma-tubulin (TUBG1; 191135) forms a ring complex that localizes to the pericentriolar matrix and nucleates microtubules for the formation of microtubule asters around centrioles. Aster microtubules then join spindle microtubules emanating from sister chromatids to generate the tension required for chromosome segregation. Using RNA interference experiments in human cell lines, Oshimori et al. (2009) found that CEP72 was essential for the structural integrity of the centrosome and for aster formation during mitosis. In the absence of CEP72, several critical centrosomal proteins, including KIZ (615757), CGNAP (AKAP9; 604001), and TUBG1, were not targeted to centrosomes, and spindle microtubules did not join aster microtubules for chromosome alignment at the metaphase plate.
By coimmunoprecipitation analysis, Stowe et al. (2012) found that CEP72 interacted directly with PCM1 in polarized mouse and human cells. CEP72 also interacted with CEP290 (610142). Depletion of PCM1 in both ciliated and nonciliated cells resulted in microtubule-independent relocalization of CEP72 and CEP290 from centrosomal satellites to centrosomes. Depletion of either CEP72 or CEP290 reduced pericentrosomal PCM1 and reduced cilium formation in RPE1 cells. Reduced cilium formation in ciliated mouse and human cells coincided with reduced ciliary recruitment of BBS4 (600374) and BBS8 (TTC8; 608132), subunits of the BBS protein complex required for formation of primary cilia. Overexpression of CEP72 disrupted organization of centriolar satellites and interfered with formation of the primary cilium.
Stowe et al. (2012) stated that the CEP72 gene maps to chromosome 5p15.33.
Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 143-150, 2000. [PubMed: 10819331] [Full Text: https://doi.org/10.1093/dnares/7.2.143]
Oshimori, N., Li, X., Ohsugi, M., Yamamoto, T. Cep72 regulates the localization of key centrosomal proteins and proper bipolar spindle formation. EMBO J. 28: 2066-2076, 2009. [PubMed: 19536135] [Full Text: https://doi.org/10.1038/emboj.2009.161]
Stowe, T. R., Wilkinson, C. J., Iqbal, A., Stearns, T. The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium. Molec. Biol. Cell 23: 3322-3335, 2012. [PubMed: 22767577] [Full Text: https://doi.org/10.1091/mbc.E12-02-0134]