PSIP1

PC4 and SFRS1 interacting protein 1

PDB rendering based on 1z9e.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsPSIP1 ; DFS70; LEDGF; PAIP; PSIP2; p52; p75
External IDsOMIM: 603620 MGI: 2142116 HomoloGene: 13242 GeneCards: PSIP1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez11168101739
EnsemblENSG00000164985ENSMUSG00000028484
UniProtO75475Q99JF8
RefSeq (mRNA)NM_001128217NM_001290527
RefSeq (protein)NP_001121689NP_001277456
Location (UCSC)Chr 9:
15.46 – 15.51 Mb		Chr 4:
83.46 – 83.49 Mb
PubMed search

PC4 and SFRS1 interacting protein 1, also known as lens epithelium-derived growth factor (LEDGF/p75), dense fine speckles 70kD protein (DFS 70) or transcriptional coactivator p75/p52, is a protein that in humans is encoded by the PSIP1 gene.[1][2]

Function

PSIP1 has not been clearly linked to a specific cellular mechanism. The term LEDGF/p75 (Lens epithelium-derived growth factor) has entered common usage based on the initial characterization of PSIP1, however this is a misnomer, as the protein is present in most tissues and has no direct role in the development of lens epithelium. LEDGF/p75, a transcription coactivator, gained prominence as a host factor that assists HIV integration[3] and is probably the only integrase interactor whose knock-down severely affects the HIV integration levels.[4][5][6] The interaction between HIV integrase and human LEDGF/p75 is a promising target for anti-HIV drug discovery.[7]

Structure

LEDGF/p75 is a 60kDa, 530-amino-acid-long protein.[8] The N-terminal portion of the protein consists of a PWWP domain, a nuclear localization sequence, and two copies of the AT-hook DNA binding motif. The C-terminal portion of LEDGF/p75 contains a structure termed the integrase-binding domain,[9] which interacts with lentiviral integrase proteins as well as numerous cellular proteins. The N-terminal portion interacts strongly with chromatin, making LEDGF/p75 a constitutively nuclear protein. An isoform of the protein, LEDGF/p52, is produced by alternative splicing. LEDGF/p52 shares the N-terminal 325 amino acids of LEDGF/p75 but lacks the integrase-binding domain.

Interactions

PSIP1 has been shown to interact with the proteins ASF/SF2, JPO2, Cdc7-Dbf4, and POGZ as well as the menin/MLL protein complex.[10][11]

References

  1. ↑ "Entrez Gene: PSIP1 PC4 and SFRS1 interacting protein 1".
  2. ↑ Singh DP, Kimura A, Chylack LT, Shinohara T (January 2000). "Lens epithelium-derived growth factor (LEDGF/p75) and p52 are derived from a single gene by alternative splicing". Gene 242 (1-2): 265–73. doi:10.1016/S0378-1119(99)00506-5. PMID 10721720.
  3. ↑ Cherepanov P, Maertens G, Proost P, Devreese B, Van Beeumen J, Engelborghs Y et al. (January 2003). "HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells". J. Biol. Chem. 278 (1): 372–81. doi:10.1074/jbc.M209278200. PMID 12407101.
  4. ↑ Vandekerckhove L, Christ F, Van Maele B, De Rijck J, Gijsbers R, Van den Haute C et al. (February 2006). "Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus". J. Virol. 80 (4): 1886–96. doi:10.1128/JVI.80.4.1886-1896.2006. PMC 1367129. PMID 16439544.
  5. ↑ Shun MC, Raghavendra NK, Vandegraaff N, Daigle JE, Hughes S, Kellam P et al. (July 2007). "LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration". Genes Dev. 21 (14): 1767–78. doi:10.1101/gad.1565107. PMC 1920171. PMID 17639082.
  6. ↑ Llano M, Saenz DT, Meehan A, Wongthida P, Peretz M, Walker WH et al. (October 2006). "An essential role for LEDGF/p75 in HIV integration". Science 314 (5798): 461–4. doi:10.1126/science.1132319. PMID 16959972.
  7. ↑ Christ F, Voet A, Marchand A, Nicolet S, Desimmie BA, Marchand D et al. (June 2010). "Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication". Nat. Chem. Biol. 6 (6): 442–8. doi:10.1038/nchembio.370. PMID 20473303.
  8. ↑ Llano M, Morrison J, Poeschla EM (2009). "Virological and cellular roles of the transcriptional coactivator LEDGF/p75". Curr. Top. Microbiol. Immunol. 339: 125–46. doi:10.1007/978-3-642-02175-6_7. PMC 3093762. PMID 20012527.
  9. ↑ Cherepanov P, Sun ZY, Rahman S, Maertens G, Wagner G, Engelman A (June 2005). "Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75". Nat. Struct. Mol. Biol. 12 (6): 526–32. doi:10.1038/nsmb93. PMID 15895093.
  10. ↑ Ge H, Si Y, Wolffe AP (December 1998). "A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2". Mol. Cell 2 (6): 751–9. doi:10.1016/S1097-2765(00)80290-7. PMID 9885563.
  11. ↑ Hughes S, Jenkins V, Dar MJ, Engelman A, Cherepanov P (January 2010). "Transcriptional co-activator LEDGF interacts with Cdc7-activator of S-phase kinase (ASK) and stimulates its enzymatic activity". J. Biol. Chem. 285 (1): 541–54. doi:10.1074/jbc.M109.036491. PMC 2804203. PMID 19864417.

Further reading