| Written | 2007-03 | Cristina Morerio, Claudio Panarello |
| Dipartimento di Ematologia ed Oncologia Pediatrica, IRCCS Istituto Giannina Gaslini, Largo G. Gaslini 5, 16147 Genoa, Italy |
| Identity |
| Alias_names | PSIP2 |
| PC4 and SFRS1 interacting protein 2 | |
| Alias_symbol (synonym) | p52 |
| LEDGF | |
| p75 | |
| DFS70 | |
| Other alias | LEDGF (lens epithelium-derived growth factor) |
| HGNC (Hugo) | PSIP1 |
| LocusID (NCBI) | 11168 |
| Atlas_Id | 405 |
| Location | 9p22.3 [Link to chromosome band 9p22] |
| Location_base_pair | Starts at 15464066 and ends at 15511019 bp from pter ( according to hg19-Feb_2009) [Mapping PSIP1.png] |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| LYRM4 (6p25.1) / PSIP1 (9p22.3) | NUP98 (11p15.4) / PSIP1 (9p22.3) | PSIP1 (9p22.3) / MYL6 (12q13.2) | |
| PSIP1 (9p22.3) / NUP98 (11p15.4) | PSIP1 (9p22.3) / PSIP1 (9p22.3) | QPCTL (19q13.32) / PSIP1 (9p22.3) | |
| DNA/RNA |
| Description | The gene contains at least 15 exons and 14 introns. |
| Transcription | Two alternative splice variants: p75 and p52. |
| Protein |
| Description | 530 amino acids (p75), 333 amino acids (p52); N-term - PWWP (proline-tryptophan-tryptophan-proline) domain NLS (nuclear localization signal) AT-hook-like Coiled coil IBD (integrase binding domain) HTH1 (helix-turn-helix DNA binding motif) HTH2 C-term. |
| Expression | Expression of PSIP1 has been reported to be increased in human breast and bladder cancer, prostate tumorsand benign prostate hyperplasia. |
| Localisation | nuclear. |
| Function | Transcriptional regulation of stress-associated genes, mRNA splicing and cell survival. The involvement of PSIP1 (LEDGF) has been reported in human immunodeficiency virus type-1 (HIV-1) integration, autoimmune disorders, and neurogenesis. Recent data reveal LEDGF as an oncogenic protein that controls a caspase-independent lysosomal cell death pathway. |
| Homology | PSIP1 belongs to the hepatoma-derived growth factor (HDGF) family of proteins that contain a well conserved N-terminal amino acid sequence known as the HATH (homologous to amino terminus of HDGF) region. |
| Implicated in |
| Note | |
| Entity | t(9;11)(p22;p15) NUP98-PSIP1 |
| Note | acute non lymphoblastic leukemia (AML), one case of transformed |
| Hybrid/Mutated Gene | 5'NUP98 - 3'PSIP1. |
| Abnormal Protein | fuses the GLFG repeat domains of NUP98 to the COOH-terminus of PSIP1. |
| Bibliography |
| t(9;11)(p22;p15) in acute myeloid leukemia results in a fusion between NUP98 and the gene encoding transcriptional coactivators p52 and p75-lens epithelium-derived growth factor (LEDGF). |
| Ahuja HG, Hong J, Aplan PD, Tcheurekdjian L, Forman SJ, Slovak ML |
| Cancer research. 2000 ; 60 (22) : 6227-6229. |
| PMID 11103774 |
| HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells. |
| Cherepanov P, Maertens G, Proost P, Devreese B, Van Beeumen J, Engelborghs Y, De Clercq E, Debyser Z |
| The Journal of biological chemistry. 2003 ; 278 (1) : 372-381. |
| PMID 12407101 |
| Antinuclear autoantibodies in prostate cancer: immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis. |
| Daniels T, Zhang J, Gutierrez I, Elliot ML, Yamada B, Heeb MJ, Sheets SM, Wu X, Casiano CA |
| The Prostate. 2005 ; 62 (1) : 14-26. |
| PMID 15389814 |
| Lens epithelium-derived growth factor is an Hsp70-2 regulated guardian of lysosomal stability in human cancer. |
| Daugaard M, Kirkegaard-S&oring;rensen T, Ostenfeld MS, Aaboe M, H&oring;yer-Hansen M, Orntoft TF, Rohde M, Jäättelä M |
| Cancer research. 2007 ; 67 (6) : 2559-2567. |
| PMID 17363574 |
| NUP98-LEDGF fusion and t(9;11) in transformed chronic myeloid leukemia. |
| Grand FH, Koduru P, Cross NC, Allen SL |
| Leukemia research. 2005 ; 29 (12) : 1469-1472. |
| PMID 15982735 |
| Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation. |
| Hussey DJ, Moore S, Nicola M, Dobrovic A |
| BMC genetics. 2001 ; 2 : page 20. |
| PMID 11737860 |
| t(9;11)(p22;p15) with NUP98-LEDGF fusion gene in pediatric acute myeloid leukemia. |
| Morerio C, Acquila M, Rosanda C, Rapella A, Tassano E, Micalizzi C, Panarello C |
| Leukemia research. 2005 ; 29 (4) : 467-470. |
| PMID 15725483 |
| Lens epithelium-derived growth factor (LEDGF/p75) and p52 are derived from a single gene by alternative splicing. |
| Singh DP, Kimura A, Chylack LT Jr, Shinohara T |
| Gene. 2000 ; 242 (1-2) : 265-273. |
| PMID 10721720 |
| DNA binding domains and nuclear localization signal of LEDGF: contribution of two helix-turn-helix (HTH)-like domains and a stretch of 58 amino acids of the N-terminal to the trans-activation potential of LEDGF. |
| Singh DP, Kubo E, Takamura Y, Shinohara T, Kumar A, Chylack LT Jr, Fatma N |
| Journal of molecular biology. 2006 ; 355 (3) : 379-394. |
| PMID 16318853 |
| Disruption of Ledgf/Psip1 results in perinatal mortality and homeotic skeletal transformations. |
| Sutherland HG, Newton K, Brownstein DG, Holmes MC, Kress C, Semple CA, Bickmore WA |
| Molecular and cellular biology. 2006 ; 26 (19) : 7201-7210. |
| PMID 16980622 |
| Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders. |
| Wu X, Daniels T, Molinaro C, Lilly MB, Casiano CA |
| Cell death and differentiation. 2002 ; 9 (9) : 915-925. |
| PMID 12181742 |
| Citation |
| This paper should be referenced as such : |
| Panarello, C ; Morerio, C |
| PSIP1 (PC4, SFRS1 interacting protein 1) |
| Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):237-238. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/PSIP1ID405ch9q22.html |
| Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
t(9;11)(p22;p15) NUP98/PSIP1
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| 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 Nov 13 21:51:58 CET 2019 |
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