Retinoblastoma protein: Difference between revisions

Jump to navigation Jump to search
← Older editNewer edit →
VisualWikitext
Brian Blank (talk | contribs)
nocaptcha
2,344 edits
No edit summary
WikiBot (talk | contribs)
Bots, Bureaucrats, bureaucrats, interwiki, nocaptcha, Administrators
57,550 edits
m Robot: Automated text replacement (-{{SIB}} +, -{{EH}} +, -{{EJ}} +, -{{Editor Help}} +, -{{Editor Join}} +)
Line 48: Line 48:
   }}
   }}
}}
}}
{{EH}}
 
==Overview==
==Overview==
The '''retinoblastoma protein''', also called '''pRb''' or '''''Rb''''', is a [[tumor suppressor gene|tumor suppressor]] [[protein]] found to be dysfunctional in a number of types of [[cancer]].<ref name="Murphree1984">Murphree A.L. and Benedict W.F. 1984. Retinoblastoma: clues to human oncogenesis in ''[[Science (journal)|Science]]'', 223(4640): 1028-1033. {{Entrez Pubmed|6320372}} Retrieved on January 24, 2007.</ref> pRb was so named because [[retinoblastoma]] cancer results when the protein is inactivated by a mutation in both [[allele]]s of the [[RB1]] gene that [[code for|codes for]] it. The "p" in pRb stands for protein and is a way to distinguish it from the gene, ''Rb''.  pRb is usually present as a [[phosphoprotein]] inside cells and is a target for [[phosphorylation]] by several [[kinase]]s as described [[#Activation and inactivation|below]]. One highly studied function of pRb is to prevent the [[cell (biology)|cell]] from dividing or progressing through the [[cell cycle]].  Thus, when pRb is ineffective at this role, [[mutation|mutated]] cells can continue to divide and may become cancerous.
The '''retinoblastoma protein''', also called '''pRb''' or '''''Rb''''', is a [[tumor suppressor gene|tumor suppressor]] [[protein]] found to be dysfunctional in a number of types of [[cancer]].<ref name="Murphree1984">Murphree A.L. and Benedict W.F. 1984. Retinoblastoma: clues to human oncogenesis in ''[[Science (journal)|Science]]'', 223(4640): 1028-1033. {{Entrez Pubmed|6320372}} Retrieved on January 24, 2007.</ref> pRb was so named because [[retinoblastoma]] cancer results when the protein is inactivated by a mutation in both [[allele]]s of the [[RB1]] gene that [[code for|codes for]] it. The "p" in pRb stands for protein and is a way to distinguish it from the gene, ''Rb''.  pRb is usually present as a [[phosphoprotein]] inside cells and is a target for [[phosphorylation]] by several [[kinase]]s as described [[#Activation and inactivation|below]]. One highly studied function of pRb is to prevent the [[cell (biology)|cell]] from dividing or progressing through the [[cell cycle]].  Thus, when pRb is ineffective at this role, [[mutation|mutated]] cells can continue to divide and may become cancerous.
Line 105: Line 105:
[[Category:Transcription coregulators]]
[[Category:Transcription coregulators]]
[[Category:Transcription factors]]
[[Category:Transcription factors]]
{{SIB}}
 
[[es:Proteína del retinoblastoma]]
[[es:Proteína del retinoblastoma]]
[[fr:Protéine du rétinoblastome]]
[[fr:Protéine du rétinoblastome]]

Revision as of 15:41, 20 August 2012


Retinoblastoma 1 (including osteosarcoma)
PDB rendering based on 1ad6.
Available structures
PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB
Identifiers
Symbols RB1 ; OSRC; RB
External IDs Template:OMIM5 Template:MGI HomoloGene: 272
RNA expression pattern
File:PBB GE RB1 203132 at.png
File:PBB GE RB1 211540 s at.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

Overview

The retinoblastoma protein, also called pRb or Rb, is a tumor suppressor protein found to be dysfunctional in a number of types of cancer.[1] pRb was so named because retinoblastoma cancer results when the protein is inactivated by a mutation in both alleles of the RB1 gene that codes for it. The "p" in pRb stands for protein and is a way to distinguish it from the gene, Rb. pRb is usually present as a phosphoprotein inside cells and is a target for phosphorylation by several kinases as described below. One highly studied function of pRb is to prevent the cell from dividing or progressing through the cell cycle. Thus, when pRb is ineffective at this role, mutated cells can continue to divide and may become cancerous.

pRb is a member of the 'Pocket protein family', because it has a pocket to which proteins can bind.[2][3] Oncogenic proteins such as those produced by cells infected by high-risk types of human papillomaviruses can bind and inactivate pRb, which can lead to cancer.

Cell cycle suppression

pRb prevents the cell from replicating damaged DNA by preventing its progression through the cell cycle into its S, or synthesis phase or progressing through G1, or first gap phase.[4] pRb binds and inhibits transcription factors of the E2F family. E2F transcription factors are dimers of an E2F protein and a DP protein.[5] The transcription activating complexes of E2 promoter-binding–protein-dimerization partners (E2F-DP) can push a cell into S phase.[6][7][8][9][10] As long as E2F-DP is inactivated, the cell remains stalled in the G1 phase. When pRb is bound to E2F, the complex acts as a growth suppressor and prevents progression through the cell cycle.[3] The pRb-E2F/DP complex also attracts a histone deacetylase (HDAC) protein to the chromatin, further suppressing DNA synthesis.

Activation and inactivation

pRb can actively inhibit cell cycle progression when it is dephosphorylated while this function is inactivated when pRb is phosphorylated. pRb is activated near the end of G1 phase when a phosphatase dephosphorylates it, allowing it to bind E2F.[3][11]

When it is time for a cell to enter S phase, complexes of cyclin-dependent kinases (CDK) and cyclins phosphorylate pRb, inhibiting its activity.[2][3][4][12] The initial phosphorylation is performed by Cyclin D/CDK4,6 and followed by additional phosphorylation by Cyclin E/CDK2. pRb remains phosphorylated throughout S, G2 and M phases.[3]

Phosphorylation of pRb allows E2F-DP to dissociate from pRb and become active.[3][7][4] When E2F is freed it activates factors like cyclins (e.g. Cyclin E and A), which push the cell through the cell cycle by activating cyclin-dependent kinases, and a molecule called proliferating cell nuclear antigen, or PCNA, which speeds DNA replication and repair by helping to attach polymerase to DNA.[6][4][9]

See also

References

  1. ↑ Murphree A.L. and Benedict W.F. 1984. Retinoblastoma: clues to human oncogenesis in Science, 223(4640): 1028-1033. Template:Entrez Pubmed Retrieved on January 24, 2007.
  2. ↑ 2.0 2.1 Korenjak M. and Brehm A. 2005. E2F–Rb complexes regulating transcription of genes important for differentiation and development. Current Opinion in Genetics & Development, 15(5): 520-527.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Münger K. and Howley P.M. 2002. Human papillomavirus immortalization and transformation functions. Virus Research, 89: 213–228.
  4. ↑ 4.0 4.1 4.2 4.3 Das S.K., Hashimoto T., Shimizu K., Yoshida T., Sakai T., Sowa Y., Komoto A., and Kanazawa K. 2005. Fucoxanthin induces cell cycle arrest at G0/G1 phase in human colon carcinoma cells through up-regulation of p21WAF1/Cip1. Biochimica et Biophysica Acta, 1726(3):328-335. PMID 16236452. Retrieved on January 24, 2007.
  5. ↑ Wu C.L., Zukerberg L.R., Ngwu C., Harlow E. and Lees J.A. 1995. In vivo association of E2F and DP family proteins. Molecular and Cellular Biology 15(5): 2536-2546. Template:Entrez Pubmed Retrieved on January 24, 2007.
  6. ↑ 6.0 6.1 Funk J.O., Waga S., Harry J.B., Espling E., Stillman B., and Galloway D.A. 1997. Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein. Trends in Genetics, 13(12): 474.
  7. ↑ 7.0 7.1 De Veylder L., Joubès J., and Inzé D. 2003. Plant cell cycle transitions. Current Opinion in Plant Biology. 6(6): 536-543.
  8. ↑ de Jager S.M., Maughan S., Dewitte W., Scofield S., and Murray J.A.H. 2005. The developmental context of cell-cycle control in plants. Seminars in Cell & Developmental Biology. 16(3): 385-396. PMID 15840447. Retrieved on January 24, 2007.
  9. ↑ 9.0 9.1 Greenblatt R.J. 2005. Human papillomaviruses: Diseases, diagnosis, and a possible vaccine. Clinical Microbiology Newsletter, 27(18): 139-145. doi:10.1016/j.clinmicnews.2005.09.001. Retrieved on January 24, 2007.
  10. ↑ Sinal S.H. and Woods C.R. 2005. Human papillomavirus infections of the genital and respiratory tracts in young children. Seminars in Pediatric Infectious Diseases, 16(4): 306-316. PMID 16210110. Retrieved on January 24, 2007.
  11. ↑ Vietri M., Bianchi M., Ludlow J.W., Mittnacht S. and Villa-Moruzzi E. 2006. Direct interaction between the catalytic subunit of Protein Phosphatase 1 and pRb. Cancer cell international, 6(3): 3 Template:Entrez Pubmed Retrieved on January 24, 2007.
  12. ↑ Bartkova J., Grøn B., Dabelsteen E., and Bartek J. 2003. Cell-cycle regulatory proteins in human wound healing. Archives of Oral Biology, 48(2): 125-132. PMID 12642231. Retrieved on January 24, 2007.

Further reading

  • Momand J, Wu HH, Dasgupta G (2000). "MDM2--master regulator of the p53 tumor suppressor protein". Gene. 242 (1–2): 15–29. PMID 10721693.
  • Zheng L, Lee WH (2003). "Retinoblastoma tumor suppressor and genome stability". Adv. Cancer Res. 85: 13–50. PMID 12374284.
  • Classon M, Harlow E (2003). "The retinoblastoma tumour suppressor in development and cancer". Nat. Rev. Cancer. 2 (12): 910–7. doi:10.1038/nrc950. PMID 12459729.
  • Lai H, Ma F, Lai S (2003). "Identification of the novel role of pRB in eye cancer". J. Cell. Biochem. 88 (1): 121–7. doi:10.1002/jcb.10283. PMID 12461781.
  • Simin K, Wu H, Lu L; et al. (2006). "pRb inactivation in mammary cells reveals common mechanisms for tumor initiation and progression in divergent epithelia". PLoS Biol. 2 (2): E22. doi:10.1371/journal.pbio.0020022. PMID 14966529.
  • Lohmann DR, Gallie BL (2004). "Retinoblastoma: revisiting the model prototype of inherited cancer". American journal of medical genetics. Part C, Seminars in medical genetics. 129 (1): 23–8. doi:10.1002/ajmg.c.30024. PMID 15264269.
  • Clemo NK, Arhel NJ, Barnes JD; et al. (2005). "The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival". Biochem. Soc. Trans. 33 (Pt 4): 676–8. doi:10.1042/BST0330676. PMID 16042572.
  • Rodríguez-Cruz M, del Prado M, Salcedo M (2006). "[Genomic retinoblastoma perspectives: implications of tumor supressor gene RB1]". Rev. Invest. Clin. 57 (4): 572–81. PMID 16315642.
  • Knudsen ES, Knudsen KE (2006). "Retinoblastoma tumor suppressor: where cancer meets the cell cycle". Exp. Biol. Med. (Maywood). 231 (7): 1271–81. PMID 16816134.


External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

it:Proteina del retinoblastoma

Template:WH

Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Retinoblastoma_protein&oldid=687916"