4aif

Structural highlights

Disease

[AIP_HUMAN] Acromegaly;Familial prolactinoma. Defects in AIP are a cause of growth hormone-secreting pituitary adenoma (GHSPA) [MIM:102200]; also known as familial isolated somatotropinomas (FIS) or isolated familial somatotropinoma (IFS) or familial somatotrophinoma or acromegaly due to pituitary adenoma.^{[1] [2] [3] [4]} Defects in AIP are a cause of ACTH-secreting pituitary adenoma (ASPA) [MIM:219090]; also known as pituitary Cushing disease. A pituary adenoma resulting in excessive production of adrenocorticotropic hormone. This leads to hypersecretion of cortisol by the adrenal glands and ACTH-dependent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and trunkal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. Defects in AIP are a cause of prolactin-secreting pituitary adenoma (PSPA) [MIM:600634]; also known as prolactinoma. Prolactin-secreting pituitary adenoma is the most common type of hormonally active pituitary adenoma.

Function

[AIP_HUMAN] May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting. Cellular negative regulator of the hepatitis B virus (HBV) X protein. [HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.^{[5] [6]}

References

1. ↑ Daly AF, Vanbellinghen JF, Khoo SK, Jaffrain-Rea ML, Naves LA, Guitelman MA, Murat A, Emy P, Gimenez-Roqueplo AP, Tamburrano G, Raverot G, Barlier A, De Herder W, Penfornis A, Ciccarelli E, Estour B, Lecomte P, Gatta B, Chabre O, Sabate MI, Bertagna X, Garcia Basavilbaso N, Stalldecker G, Colao A, Ferolla P, Wemeau JL, Caron P, Sadoul JL, Oneto A, Archambeaud F, Calender A, Sinilnikova O, Montanana CF, Cavagnini F, Hana V, Solano A, Delettieres D, Luccio-Camelo DC, Basso A, Rohmer V, Brue T, Bours V, Teh BT, Beckers A. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab. 2007 May;92(5):1891-6. Epub 2007 Jan 23. PMID:17244780 doi:jc.2006-2513
2. ↑ Barlier A, Vanbellinghen JF, Daly AF, Silvy M, Jaffrain-Rea ML, Trouillas J, Tamagno G, Cazabat L, Bours V, Brue T, Enjalbert A, Beckers A. Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas. J Clin Endocrinol Metab. 2007 May;92(5):1952-5. Epub 2007 Feb 13. PMID:17299063 doi:jc.2006-2702
3. ↑ Georgitsi M, Raitila A, Karhu A, Tuppurainen K, Makinen MJ, Vierimaa O, Paschke R, Saeger W, van der Luijt RB, Sane T, Robledo M, De Menis E, Weil RJ, Wasik A, Zielinski G, Lucewicz O, Lubinski J, Launonen V, Vahteristo P, Aaltonen LA. Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4101-5. Epub 2007 Feb 28. PMID:17360484 doi:0700004104
4. ↑ Georgitsi M, De Menis E, Cannavo S, Makinen MJ, Tuppurainen K, Pauletto P, Curto L, Weil RJ, Paschke R, Zielinski G, Wasik A, Lubinski J, Vahteristo P, Karhu A, Aaltonen LA. Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas. Clin Endocrinol (Oxf). 2008 Oct;69(4):621-7. Epub 2008 Apr 10. PMID:18410548 doi:CEN3266
5. ↑ Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. PMID:15937123 doi:10.1073/pnas.0407294102
6. ↑ Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. PMID:11274138 doi:10.1074/jbc.C100055200
7. ↑ Morgan RM, Hernandez-Ramirez LC, Trivellin G, Zhou L, Roe SM, Korbonits M, Prodromou C. Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition. PLoS One. 2012;7(12):e53339. doi: 10.1371/journal.pone.0053339. Epub 2012 Dec 31. PMID:23300914 doi:http://dx.doi.org/10.1371/journal.pone.0053339