Alternative titles; symbols
HGNC Approved Gene Symbol: PCLAF
Cytogenetic location: 15q22.31 Genomic coordinates (GRCh38) : 15:64,364,304-64,387,687 (from NCBI)
By sequencing clones obtained from a size-fractionated immature myeloid leukemia cell line cDNA library, Nagase et al. (1995) cloned KIAA0101. The deduced protein contains 111 amino acids. Northern blot analysis detected high expression in thymus and colon, intermediate expression in placenta, liver, kidney, spleen, ovary, small intestine, and peripheral blood leukocytes, weak expression in lung, pancreas, and testis, and no expression in heart, brain, skeletal muscle, and prostate. Expression was also detected in HeLa cells.
Using PCNA (176740) as bait in a yeast 2-hybrid screen of a cDNA library derived from adult and fetal brain, thalamus, and hippocampus, Yu et al. (2001) cloned p15(PAF). The predicted 15-kD protein contains a central PCNA-binding motif. Northern blot analysis detected a 1.1-kb transcript in liver, pancreas, and placenta, but not in heart, brain, or lung. Fluorescence-tagged p15(PAF) localized mainly to nuclei of transfected HeLa cells.
By semiquantitative PCR, Mizutani et al. (2005) found weak but ubiquitous OEATC1 expression.
By coimmunoprecipitation analysis, Yu et al. (2001) showed that p15(PAF) bound endogenous PCNA in human embryonic kidney 293 cells, and mutation analysis indicated that ile65 and phe68 of p15(PAF) were required for the interaction. Overexpressed p15(PAF) competed with p21(WAF1) (CDKN1A; 116899) for PCNA binding in 293 cells. Expression of p15(PAF) was significantly increased in several types of tumor tissues, particularly in esophageal tumors.
Simpson et al. (2006) found that epitope-tagged p15(PAF) showed nuclear and mitochondrial localization, with the proportion in each compartment depending upon the cell line transfected. Endogenous p15(PAF) colocalized with PCNA in mouse skin and in human colon sections, but not in cultured cells. Western blot analysis showed that low-level ultraviolet (UV) irradiation increased expression of p15(PAF) in several human cell lines, and immunofluorescence microscopy revealed that p15(PAF) staining increased in both nucleus and mitochondria following irradiation. p33ING1b (ING1; 601566) coimmunoprecipitated with p15(PAF) in both untreated and UV-irradiated cells, and PCNA coimmunoprecipitated with p33ING1B and p15(PAF) in UV-irradiated cells. Simpson et al. (2006) concluded that p15(PAF) constitutively associates with p33ING1B, and that the association of both p15(PAF) and p33ING1B with PCNA is enhanced by UV treatment.
Using microarray analysis, Mizutani et al. (2005) found that OEATC1 was overexpressed in anaplastic thyroid carcinoma cell lines compared with normal thyroid tissue. Knockdown of OEATC1 by small interfering RNA in an anaplastic thyroid cancer cell line significantly reduced cell growth.
By PCR of human-rodent hybrid cell lines, Nagase et al. (1995) mapped the KIAA0101 gene to chromosome 15. Mizutani et al. (2005) mapped the OEATC1 gene to chromosome 15q22.1 by genomic sequence analysis.
Mizutani, K., Onda, M., Asaka, S., Akaishi, J., Miyamoto, S., Yoshida, A., Nagahama, M., Ito, K., Emi, M. Overexpressed in anaplastic thyroid carcinoma-1 (OEATC-1) as a novel gene responsible for anaplastic thyroid carcinoma. Cancer 103: 1785-1790, 2005. [PubMed: 15789362] [Full Text: https://doi.org/10.1002/cncr.20988]
Nagase, T, Miyajima, N, Tanaka, A., Sazuka, T., Seki, N., Sato, S., Tabata, S., Ishikawa, K., Kawarabayashi, Y., Kotani, H., Nomura, N. Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 2: 37-43, 1995. [PubMed: 7788527] [Full Text: https://doi.org/10.1093/dnares/2.1.37]
Simpson, F., Lammerts van Bueren, K., Butterfield, N., Bennetts, J. S., Bowles, J., Adolphe, C., Simms, L. A., Young, J., Walsh, M. D., Leggett, B., Fowles, L. F., Wicking, C. The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b. Exp. Cell Res. 312: 73-85, 2006. [PubMed: 16288740] [Full Text: https://doi.org/10.1016/j.yexcr.2005.09.020]
Yu, P., Huang, B., Shen, M., Lau, C., Chan, E., Michel, J., Xiong, Y., Payan, D. G., Luo, Y. p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues. Oncogene 20: 484-489, 2001. [PubMed: 11313979] [Full Text: https://doi.org/10.1038/sj.onc.1204113]