AH receptor-interacting protein explained

AH receptor-interacting protein (AIP) also known as aryl hydrocarbon receptor-interacting protein, immunophilin homolog ARA9, or HBV X-associated protein 2 (XAP-2) is a protein that in humans is encoded by the AIP gene.^{[1] [2] [3]} The protein is a member of the FKBP family.

Function

AIP may play a positive role in aryl hydrocarbon receptor-mediated signalling possibly by influencing its receptivity for ligand and/or its nuclear targeting. AIP is the cellular negative regulator of the hepatitis B virus (HBV) X protein.^[1] Further, it's been known to suppress antiviral signaling and the induction of type I interferon by targeting IRF7, a key player in the antiviral signal pathways.^[4] AIP consists of an N-terminal FKBP52 like domain and a C-terminal TPR domain. ^[5]

Mutations and role in disease

AIP mutations may be the cause of a familial form of acromegaly, familial isolated pituitary adenoma (FIPA). Somatotropinomas (i.e. GH-producing pituitary adenomas), sometimes associated with prolactinomas, are present in most AIP mutated patients.^[6]

Interactions

AIP has been shown to interact with the aryl hydrocarbon receptor,^{[3] [7] [8]} peroxisome proliferator-activated receptor alpha^[9] and the aryl hydrocarbon receptor nuclear translocator.^{[3] [10]} Further, it has shown that AIP can interact with IRF7 to exert its novel function of negatively regulating antiviral signal pathways.

Further reading

• Zhou Q, Lavorgna A . Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon. . Journal of Biological Chemistry . 2015 . 290 . 23 . 14729–14739 . 10.1074/jbc.M114.633065 . 25911105 . etal. 4505538 . free .
• Chen HS, Perdew GH . Subunit composition of the heteromeric cytosolic aryl hydrocarbon receptor complex. . J. Biol. Chem. . 269 . 44 . 27554–8 . 1994 . 10.1016/S0021-9258(18)47020-2 . 7961671 . free .
• Ma Q, Whitlock JP . A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin. . J. Biol. Chem. . 272 . 14 . 8878–84 . 1997 . 9083006 . 10.1074/jbc.272.14.8878 . free .
• Meyer BK, Pray-Grant MG, Vanden Heuvel JP, Perdew GH . Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity. . Mol. Cell. Biol. . 18 . 2 . 978–88 . 1998 . 9447995 . 108810 . 10.1128/MCB.18.2.978.
• Carver LA, LaPres JJ, Jain S . Characterization of the Ah receptor-associated protein, ARA9. . J. Biol. Chem. . 273 . 50 . 33580–7 . 1999 . 9837941 . 10.1074/jbc.273.50.33580 . etal. free .
• Gadelha MR, Une KN, Rohde K . Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12. . J. Clin. Endocrinol. Metab. . 85 . 2 . 707–14 . 2000 . 10.1210/jcem.85.2.6386 . 10690880 . etal. free .
• Petrulis JR, Hord NG, Perdew GH . Subcellular localization of the aryl hydrocarbon receptor is modulated by the immunophilin homolog hepatitis B virus X-associated protein 2. . J. Biol. Chem. . 275 . 48 . 37448–53 . 2001 . 10986286 . 10.1074/jbc.M006873200 . free .
• Kazlauskas A, Poellinger L, Pongratz I . The immunophilin-like protein XAP2 regulates ubiquitination and subcellular localization of the dioxin receptor. . J. Biol. Chem. . 275 . 52 . 41317–24 . 2001 . 11013261 . 10.1074/jbc.M007765200 . free .
• Kazlauskas A, Sundström S, Poellinger L, Pongratz I . The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor. . Mol. Cell. Biol. . 21 . 7 . 2594–607 . 2001 . 11259606 . 86890 . 10.1128/MCB.21.7.2594-2607.2001 .
• Kazlauskas A, Poellinger L, Pongratz I . Two distinct regions of the immunophilin-like protein XAP2 regulate dioxin receptor function and interaction with hsp90. . J. Biol. Chem. . 277 . 14 . 11795–801 . 2002 . 11805120 . 10.1074/jbc.M200053200 . free .
• Patterson CE, Gao J, Rooney AP, Davis EC . Genomic organization of mouse and human 65 kDa FK506-binding protein genes and evolution of the FKBP multigene family. . Genomics . 79 . 6 . 881–9 . 2002 . 12036304 . 10.1006/geno.2002.6777 .
• Berg P, Pongratz I . Two parallel pathways mediate cytoplasmic localization of the dioxin (aryl hydrocarbon) receptor. . J. Biol. Chem. . 277 . 35 . 32310–9 . 2002 . 12065584 . 10.1074/jbc.M203351200 . free .
• Dull AB, Carlson DB, Petrulis JR, Perdew GH . Characterization of the phosphorylation status of the hepatitis B virus X-associated protein 2. . Arch. Biochem. Biophys. . 406 . 2 . 209–21 . 2002 . 12361709 . 10.1016/S0003-9861(02)00444-7 .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . etal. free .
• Sumanasekera WK, Tien ES, Turpey R . Evidence that peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein and the hepatitis virus B X-associated protein 2. . J. Biol. Chem. . 278 . 7 . 4467–73 . 2003 . 12482853 . 10.1074/jbc.M211261200 . etal. free .
• Zhao Y, Meng XM, Wei YJ . Cloning and characterization of a novel cardiac-specific kinase that interacts specifically with cardiac troponin I. . J. Mol. Med. . 81 . 5 . 297–304 . 2004 . 12721663 . 10.1007/s00109-003-0427-x . 13468188 . etal.
• Lees MJ, Peet DJ, Whitelaw ML . Defining the role for XAP2 in stabilization of the dioxin receptor. . J. Biol. Chem. . 278 . 38 . 35878–88 . 2003 . 12837759 . 10.1074/jbc.M302430200 . free .
• Yano M, Terada K, Mori M . AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins. . J. Cell Biol. . 163 . 1 . 45–56 . 2003 . 14557246 . 2173431 . 10.1083/jcb.200305051 .
• Ramadoss P, Petrulis JR, Hollingshead BD . Divergent roles of hepatitis B virus X-associated protein 2 (XAP2) in human versus mouse Ah receptor complexes. . Biochemistry . 43 . 3 . 700–9 . 2004 . 14730974 . 10.1021/bi035827v . etal.
• Occhi G, Trivellin G, Ceccato F . Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia. . Eur. J. Endocrinol. . 2010 . 163 . 3 . 369–376 . 10.1530/EJE-10-0327 . 20530095 . etal . free .

Notes and References

1. Web site: Entrez Gene: AIP aryl hydrocarbon receptor interacting protein.
2. Kuzhandaivelu N, Cong YS, Inouye C, Yang WM, Seto E . XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation . Nucleic Acids Res. . 24 . 23 . 4741–50 . December 1996 . 8972861 . 146319 . 10.1093/nar/24.23.4741.
3. Carver LA, Bradfield CA . Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo . J. Biol. Chem. . 272 . 17 . 11452–6 . April 1997 . 9111057 . 10.1074/jbc.272.17.11452 . free .
4. Zhou Q, Lavorgna A, Bowman M, Hiscott J, Harhaj EW . Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon . The Journal of Biological Chemistry . 290 . 23 . 14729–39 . June 2015 . 25911105 . 10.1074/jbc.M114.633065 . 4505538 . free .
5. Petrulis JR, Perdew GH . The role of chaperone proteins in the aryl hydrocarbon receptor core complex . Chemico-Biological Interactions . 141 . 1–2 . 25–40 . 2002 . 12213383 . 10.1016/S0009-2797(02)00064-9 . 2002CBI...141...25P .
6. Occhi G, Trivellin G, Ceccato F . Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia. . Eur. J. Endocrinol. . 2010 . 163 . 3 . 369–376 . 10.1530/EJE-10-0327 . 20530095 . etal . free .
7. Petrulis JR, Hord NG, Perdew GH . Subcellular localization of the aryl hydrocarbon receptor is modulated by the immunophilin homolog hepatitis B virus X-associated protein 2 . J. Biol. Chem. . 275 . 48 . 37448–53 . December 2000 . 10986286 . 10.1074/jbc.M006873200 . free .
8. Ma Q, Whitlock JP . A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin . J. Biol. Chem. . 272 . 14 . 8878–84 . April 1997 . 9083006 . 10.1074/jbc.272.14.8878. free .
9. Sumanasekera WK, Tien ES, Turpey R, Vanden Heuvel JP, Perdew GH . Evidence that peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein and the hepatitis virus B X-associated protein 2 . J. Biol. Chem. . 278 . 7 . 4467–73 . February 2003 . 12482853 . 10.1074/jbc.M211261200 . free .
10. Kazlauskas A, Sundström S, Poellinger L, Pongratz I . The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor . Mol. Cell. Biol. . 21 . 7 . 2594–607 . April 2001 . 11259606 . 86890 . 10.1128/MCB.21.7.2594-2607.2001 .