| Written | 2006-12 | Ulla Vogel |
| National Research Centre for the Working Environment, Lersø Parkalle 105, DK-2100 Copenhagen O, Denmark |
| Identity |
| Other names | RAI (relA associated inhibitor) |
| IASPP (Inhibitor of ASPP protein) | |
| HGNC (Hugo) | PPP1R13L |
| LocusID (NCBI) | 10848 |
| Atlas_Id | 42997 |
| Location | 19q13.32 [Link to chromosome band 19q13] |
| Location_base_pair | Starts at 45882892 and ends at 45909607 bp from pter ( according to hg19-Feb_2009) [Mapping PPP1R13L.png] |
| Fusion genes (updated 2016) | BICD1 (12p11.21) / PPP1R13L (19q13.32) | CCDC120 (Xp11.23) / PPP1R13L (19q13.32) | PPP1R13L (19q13.32) / OPA3 (19q13.32) |
| PPP6R2 (22q13.33) / PPP1R13L (19q13.32) |
| DNA/RNA |
| Description | 26,674 bp 13 exons. |
| Transcription | 3,076 bps. |
| Protein |
| Description | 828 amino acids. |
| Function | PPP1R13L was originally named RAI, an acronym for RelA associated inhibitor. It was originally identified by yeast two-hybrid screening using RelA as bait. PPP1R13L was shown to associate specifically with relA and inhibit relA mediated NF-kappaB activated transcription when NF-kappaB specific transcription was activated by TNF. Yang et al. found no interaction with p53. The mRNA expression was examined in several tissues and was found to be high in heart, placenta, prostate tissues and detectable in lung, kidney, pancreas, spleen thymus, ovary, small intestine and colon. Bergamaschi et al found that PPP1R13L interacts with p53. Antisense RNA or RNAi mediated down regulation of PPP1R13L expression and induced apoptosis. Increased expression of PPP1R13L lead to increased resistance towards cisplatin and UV-induced apoptosis. This indicates that RAI inhibits apoptosis. Several studies provide evidence that PPP1R13L expression is increased in tumor tissue. In a study of colorectal adenomas and colorectal cancers, PPP1R13L expression was found to be substantially higher in lesions than in the normal tissue from the same patient. PPP1R13L expression has also been found to be increased in breast carcinomas and in blood cells in patients with acute leukemia. In a prospective study of lung cancer among 265 lung cancer cases and 272 controls nested within the population based 'Diet, Cancer and Health study', PPP1R13L expression in mononuclear blood cells (isolated by buffy coat) was not associated with risk of lung cancer. mRNA levels were found to be 41% higher in women than in men. |
| Mutations |
| Note | Genetic Epidemiology: The most frequently studied polymorphism in PPP1R13L is PPP1R13L IVS1 A4364G (rs1970764). Carriers of the variant allele have been shown to be at decreased risk of basal cell carcinoma among younger persons (< 50 years), breast cancer (<55 years) and lung cancer (<56 years). The polymorphism is part of a haplotype, which has a stronger association with risk of cancer than the polymorphism itself. Homozygous carriers of the haplotype ERCC1 Asn118AsnA, ASE-1 G-21AG, PPP1R13L IVS1 A4364GA have been shown to be at increased risk of breast cancer and lung cancer. Thus, women who were homozygous carriers of the haplotype ERCC1 Asn118AsnA, ASE-1 G-21AG, RAI IVS1 A4364GA, had a 9.5-fold higher risk of breast cancer before 55 years of age than women who were not homozygous carriers of the haplotype. Older women and heterozygous carriers were not at an increased risk of breast cancer. Homozygous carriers of the haplotype were found to be at 4.9-fold increased risk of lung cancer in the age interval 50-55 years. The association was stronger among women than among men, although the difference was not statistically significant. In subsequent study including more cases and a larger comparison group, a statistically significant difference between genders was found. Furthermore, it was found that the haplotype interacts with smoking intensity. Thus, among women, who were carriers of the haplotype, additional smoking at high smoking intensity (>20 cigarettes/day) was associated with increased lung cancer risk. This was not seen among women who were not homozygous carriers of the haplotype or among men. The haplotype was not associated with risk of testis cancer or with risk of colorectal adenomas or colorectal cancer. Furthermore, the haplotype was not associated with risk of basal cell carcinoma among older persons (>60 years). These results indicate that the haplotype may be associated with risk of cancer primarily among young and middle aged persons and that it may be specific for women. |
| Implicated in |
| Note | |
| Entity | General increased cancer risk |
| Note | No human disease has been linked to inactivation of PPP1R13L. However, polymorphisms in PPP1R13L may be associated with increased cancer risk (see above). |
| Bibliography |
| iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. |
| Bergamaschi D, Samuels Y, O'Neil NJ, Trigiante G, Crook T, Hsieh JK, O'Connor DJ, Zhong S, Campargue I, Tomlinson ML, Kuwabara PE, Lu X |
| Nature genetics. 2003 ; 33 (2) : 162-167. |
| PMID 12524540 |
| Polymorphisms in RAI and in genes of nucleotide and base excision repair are not associated with risk of testicular cancer. |
| Laska MJ, Nex&oring; BA, Vistisen K, Poulsen HE, Loft S, Vogel U |
| Cancer letters. 2005 ; 225 (2) : 245-251. |
| PMID 15885892 |
| Clinical management of women with metastatic breast cancer: a descriptive study according to age group. |
| Manders K, van de Poll-Franse LV, Creemers GJ, Vreugdenhil G, van der Sangen MJ, Nieuwenhuijzen GA, Roumen RM, Voogd AC |
| BMC cancer. 2006 ; 6 : page 179. |
| PMID 16824210 |
| A specific haplotype of single nucleotide polymorphisms on chromosome 19q13.2-3 encompassing the gene RAI is indicative of post-menopausal breast cancer before age 55. |
| Nex&oring; BA, Vogel U, Olsen A, Ketelsen T, Bukowy Z, Thomsen BL, Wallin H, Overvad K, Tj&oring;nneland A |
| Carcinogenesis. 2003 ; 24 (5) : 899-904. |
| PMID 12771034 |
| Two regions in chromosome 19q13.2-3 are associated with risk of lung cancer. |
| Vogel U, Laros I, Jacobsen NR, Thomsen BL, Bak H, Olsen A, Bukowy Z, Wallin H, Overvad K, Tj&oring;nneland A, Nex&oring; BA, Raaschou-Nielsen O |
| Mutation research. 2004 ; 546 (1-2) : 65-74. |
| PMID 14757194 |
| ERCC1, XPD and RAI mRNA levels in lymphocytes are not associated with lung cancer risk in a prospective study of Danes. |
| Vogel U, Nex&oring; BA, Tj&oring;nneland A, Wallin H, Hertel O, Raaschou-Nielsen O |
| Mutation research. 2006 ; 593 (1-2) : 88-96. |
| PMID 16054657 |
| Effect of polymorphisms in XPD, RAI, ASE-1 and ERCC1 on the risk of basal cell carcinoma among Caucasians after age 50. |
| Vogel U, Olsen A, Wallin H, Overvad K, Tj&oring;nneland A, Nex&oring; BA |
| Cancer detection and prevention. 2005 ; 29 (3) : 209-214. |
| PMID 15936590 |
| Gene-environment interactions between smoking and a haplotype of RAI, ASE-1 and ERCC1 polymorphisms among women in relation to risk of lung cancer in a population-based study. |
| Vogel U, S&oring;rensen M, Hansen RD, Tj&oring;nneland A, Overvad K, Wallin H, Nex&oring; BA, Raaschou-Nielsen O |
| Cancer letters. 2007 ; 247 (1) : 159-165. |
| PMID 16690207 |
| Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor. |
| Yang JP, Hori M, Sanda T, Okamoto T |
| The Journal of biological chemistry. 1999 ; 274 (22) : 15662-15670. |
| PMID 10336463 |
| Multiple single nucleotide polymorphisms on human chromosome 19q13.2-3 associate with risk of Basal cell carcinoma. |
| Yin J, Rockenbauer E, Hedayati M, Jacobsen NR, Vogel U, Grossman L, Bolund L, Nex&oring; BA |
| Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2002 ; 11 (11) : 1449-1453. |
| PMID 12433725 |
| The expression of iASPP in acute leukemias. |
| Zhang X, Wang M, Zhou C, Chen S, Wang J |
| Leukemia research. 2005 ; 29 (2) : 179-183. |
| PMID 15607367 |
| Citation |
| This paper should be referenced as such : |
| Vogel, U |
| PPP1R13L (protein phosphatase 1, regulatory (inhibitor) subunit 13 like) |
| Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):105-106. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/PPP1R13LID42997ch19q13.html |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Sep 28 15:50:03 CEST 2016 |
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