HGNC Approved Gene Symbol: PTENP1
Cytogenetic location: 9p13.3 Genomic coordinates (GRCh38) : 9:33,673,504-33,677,420 (from NCBI)
PTENP1 is a highly homologous processed pseudogene of the tumor suppressor gene PTEN (601728) that itself exerts a tumor suppressive function by acting as a decoy for PTEN-targeting miRNAs (Poliseno et al., 2010).
Kim et al. (1998) identified a novel homolog of PTEN, which they called PTH2, and identified only 10 amino acid substitutions compared with the PTEN coding region. However, the putative initiation codon for PTEN was changed to arginine in PTH2, leading to translation from a different initiating methionine.
Dahia et al. (1998) identified the PTEN homolog on chromosome 9p21 as a processed pseudogene. They warned that the high sequence homology of the pseudogene and the PTEN transcript may lead to misinterpretation when performing mutation analyses based on cDNA templates.
Fujii et al. (1999) found psi-PTEN to be actively transcribed. A missense mutation of the initiator methionine codon prevents translation.
Poliseno et al. (2010) stated that PTENP1 has only 18 mismatches throughout the coding sequence relative to PTEN. PTENP1 possesses a 3-prime UTR that is approximately 1 kb shorter than that of PTEN. It can be divided into 2 regions relative to its homology with the PTEN 3-prime UTR: a high homology (approximately 95%) 5-prime region and a low homology (less than 50%) 3-prime region.
By analysis of a radiation hybrid panel, Kim et al. (1998) mapped the PTENP1 gene to chromosome 9p21-q13.
Poliseno et al. (2010) stated that the PTENP1 gene is located on chromosome 9p13.3.
Poliseno et al. (2010) described the functional relationship between the mRNAs produced by the PTEN tumor suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. Within the high homology region of the PTENP1 3-prime UTR, Poliseno et al. (2010) found perfectly conserved seed matches for the PTEN-targeting miR17 (609416), miR21 (611020), miR214 (610721), miR19B1 (609419), and miR26 families. To measure the function of these miRNAs on both PTEN and PTENP1 expression, Poliseno et al. (2010) designed specific PCR primer sets in the nonhomologous 3-prime UTR regions. In prostate cancer cells, PTEN-targeting miRNAs miR19b and miR20a suppressed both PTEN and PTENP1 mRNA abundance. Additional experiments indicated that PTENP1 and PTEN are subject to the same miRNA-mediated, posttranscriptional regulation. The authors went on to demonstrate that the 3-prime UTR of PTENP1 has tumor suppressive activity, and observed that a data set of sporadic colon cancers included a clear population of samples with detectable copy number losses occurring specifically at the PTENP1 locus. Poliseno et al. (2010) concluded that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. Poliseno et al. (2010) extended their analysis to other cancer-related genes that possess pseudogenes, such as the oncogene KRAS (190070), and its pseudogene KRAS1P. Poliseno et al. (2010) also demonstrated that the transcripts of protein-coding genes such as PTEN are biologically active, and concluded that their findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a noncoding function for mRNAs.
Dahia, P. L. M., FitzGerald, M. G., Zhang, X., Marsh, D. J., Zheng, Z., Pietsch, T., von Deimling, A., Haluska, F. G., Haber, D. A., Eng, C. A highly conserved processed PTEN pseudogene is located on chromosome band 9p21. Oncogene 16: 2403-2406, 1998. [PubMed: 9620558] [Full Text: https://doi.org/10.1038/sj.onc.1201762]
Fujii, G. H., Morimoto, A. M., Berson, A. E., Bolen, J. B. Transcriptional analysis of the PTEN/MMAC1 pseudogene, psi-PTEN. Oncogene 18: 1765-1769, 1999. [PubMed: 10208437] [Full Text: https://doi.org/10.1038/sj.onc.1202492]
Kim, S. K., Su, L.-K., Oh, Y., Kemp, B. L., Hong, W. K., Mao, L. Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines. Oncogene 16: 89-93, 1998. [PubMed: 9467947] [Full Text: https://doi.org/10.1038/sj.onc.1201512]
Poliseno, L., Salmena, L., Zhang, J., Carver, B., Haveman, W. J., Pandolfi, P. P. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465: 1033-1038, 2010. [PubMed: 20577206] [Full Text: https://doi.org/10.1038/nature09144]