IGFBP3

IGFBP3
Proteína 3 de unión al factor de crecimiento parecido a la insulína
HUGO 5472
Símbolo IGFBP3
Símbolos alt. BP-53; IBP3
Datos genéticos
Locus Cr. 7 p13
Bases de datos
Entrez 3486
OMIM 146732
RefSeq NP_000589
UniProt P17936

La proteína 3 de unión al factor de crecimiento parecido a la insulína (IGFBP3) es una proteína codificada en humanos por el gen 'IGFBP3'.[1] [2] [3]

Contenido

Función

Este gen es uno de los miembros de la familia de proteínas de unión al factor de crecimiento parecido a la insulína (IGFBP) y codifica una proteína con un dominio IGFBP y otro dominio tiroglobulina tipo I. La proteína forma un complejo ternario con la subunidad ácido-lábil del factor de crecimiento parecido a la insulína (IGFALS) y, o bien con el factor de crecimiento parecido a la insulína tipo 1 o bien con el factor de crecimiento parecido a la insulína tipo 2. En esta forma, circula por el plasma sanguíneo prolongando la vida media de los IGFs y alterando su interacción con los receptores de la superficie celular. Se han caracterizado diversas variantes transcripcionales que codifican diferentes isoformas de la proteína.[2]

Importancia clínica

Los niveles de IGFBP3 decrecen a lo largo de la progresión del cáncer de próstata, desde la hiperplasia prostática benigna (BPH) hasta su forma metastásica.[4] Aunque, en cualquier caso, la producción de la proteína no cesa completamente. IGFBP3 es sintetizada aún, a bajo nivel, por las células cancerígenas de próstata y secretada al medio circundante. Sin embargo, en lugar de su forma completa y funcional, esta IGFBP3 secretada es una forma parcialmente degradada.[5] Esto evita que IGFBP3 se una y secuestre IGFs y los factores de crecimiento serán libres de unirse al IGF-1R y promover la supervivencia celular.

Interacciones

La proteína IGFBP3 ha demostrado ser capaz de interaccionar con:

Véase también

  • Mecasermin rinfabate

Referencias

  1. ↑ Cubbage ML, Suwanichkul A, Powell DR (July 1990). «Insulin-like growth factor binding protein-3. Organization of the human chromosomal gene and demonstration of promoter activity». J. Biol. Chem. 265 (21):  pp. 12642–9. PMID 1695633. 
  2. ↑ a b «Entrez Gene: IGFBP3 insulin-like growth factor binding protein 3».
  3. ↑ Rechler MM, Brown AL (Jun 1992). «Insulin-like growth factor binding proteins: gene structure and expression». Growth Regul 2 (2):  pp. 55–68. PMID 1283099. 
  4. ↑ Miyake H, Pollak M, Gleave ME (June 2000). «Castration-induced up-regulation of insulin-like growth factor binding protein-5 potentiates insulin-like growth factor-I activity and accelerates progression to androgen independence in prostate cancer models». Cancer Res. 60 (11):  pp. 3058–64. PMID 10850457. 
  5. ↑ Birnbaum RS, Ware JL, Plymate SR (June 1994). «Insulin-like growth factor-binding protein-3 expression and secretion by cultures of human prostate epithelial cells and stromal fibroblasts». J. Endocrinol. 141 (3):  pp. 535–40. PMID 7520932. 
  6. ↑ a b Liu, Bingrong; Weinzimer Stuart A, Gibson Tara Beers, Mascarenhas Desmond, Cohen Pinchas. «Type Ialpha collagen is an IGFBP-3 binding protein». Growth Horm. IGF Res. (Scotland) 13 (2-3):  pp. 89–97. ISSN 1096-6374. PMID 12735930. 
  7. ↑ a b c Twigg, S M; Baxter R C (Mar. 1998). «Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit». J. Biol. Chem. (UNITED STATES) 273 (11):  pp. 6074–9. ISSN 0021-9258. PMID 9497324. 
  8. ↑ a b c Firth, S M; Ganeshprasad U, Baxter R C (Jan. 1998). «Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3». J. Biol. Chem. (UNITED STATES) 273 (5):  pp. 2631–8. ISSN 0021-9258. PMID 9446566. 
  9. ↑ Ueki, I; Ooi G T, Tremblay M L, Hurst K R, Bach L A, Boisclair Y R (Jun. 2000). «Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system». Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (12):  pp. 6868–73. doi:10.1073/pnas.120172697. ISSN 0027-8424. PMID 10823924. 
  10. ↑ a b Buckway, C K; Wilson E M, Ahlsén M, Bang P, Oh Y, Rosenfeld R G (Oct. 2001). «Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding». J. Clin. Endocrinol. Metab. (United States) 86 (10):  pp. 4943–50. ISSN 0021-972X. PMID 11600567. 
  11. ↑ Cohen, P; Graves H C, Peehl D M, Kamarei M, Giudice L C, Rosenfeld R G (Oct. 1992). «Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma». J. Clin. Endocrinol. Metab. (UNITED STATES) 75 (4):  pp. 1046–53. ISSN 0021-972X. PMID 1383255. 
  12. ↑ Storch, S; Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (Dec. 2001). «Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3». FEBS Lett. (Netherlands) 509 (3):  pp. 395–8. ISSN 0014-5793. PMID 11749962. 
  13. ↑ Shi, Z; Xu W, Loechel F, Wewer U M, Murphy L J (Jun. 2000). «ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3». J. Biol. Chem. (UNITED STATES) 275 (24):  pp. 18574–80. doi:10.1074/jbc.M002172200. ISSN 0021-9258. PMID 10849447. 
  14. ↑ Loechel, F; Fox J W, Murphy G, Albrechtsen R, Wewer U M (Nov. 2000). «ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3». Biochem. Biophys. Res. Commun. (UNITED STATES) 278 (3):  pp. 511–5. doi:10.1006/bbrc.2000.3835. ISSN 0006-291X. PMID 11095942. 
  15. ↑ Weinzimer, S A; Gibson T B, Collett-Solberg P F, Khare A, Liu B, Cohen P (Apr. 2001). «Transferrin is an insulin-like growth factor-binding protein-3 binding protein». J. Clin. Endocrinol. Metab. (United States) 86 (4):  pp. 1806–13. ISSN 0021-972X. PMID 11297622. 
  16. ↑ Martin, J A; Miller B A, Scherb M B, Lembke L A, Buckwalter J A (Jul. 2002). «Co-localization of insulin-like growth factor binding protein 3 and fibronectin in human articular cartilage». Osteoarthr. Cartil. (England) 10 (7):  pp. 556–63. ISSN 1063-4584. PMID 12127836. 
  17. ↑ Gui, Y; Murphy L J (May. 2001). «Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) binds to fibronectin (FN): demonstration of IGF-I/IGFBP-3/fn ternary complexes in human plasma». J. Clin. Endocrinol. Metab. (United States) 86 (5):  pp. 2104–10. ISSN 0021-972X. PMID 11344214. 
  18. ↑ Campbell, P G; Durham S K, Suwanichkul A, Hayes J D, Powell D R (Aug. 1998). «Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3». Am. J. Physiol. (UNITED STATES) 275 (2 Pt 1):  pp. E321-31. ISSN 0002-9513. PMID 9688635. 
  19. ↑ Liu, B; Lee H Y, Weinzimer S A, Powell D R, Clifford J L, Kurie J M, Cohen P (Oct. 2000). «Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis». J. Biol. Chem. (UNITED STATES) 275 (43):  pp. 33607–13. doi:10.1074/jbc.M002547200. ISSN 0021-9258. PMID 10874028. 

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