Retinoblastoma protein

Retinoblastoma 1 (including osteosarcoma)
PDB rendering based on 1ad6.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1ad6​, 1gh6​, 1gux​, 1o9k​, 2aze​
Identifiers
Symbols	RB1 ; OSRC; RB
External IDs	Template:OMIM5 Template:MGI HomoloGene: 272
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
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

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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. 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. 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. pRb binds and inhibits transcription factors of the E2F family. E2F transcription factors are dimers of an E2F protein and a DP protein. The transcription activating complexes of E2 promoter-binding–protein-dimerization partners (E2F-DP) can push a cell into S phase. 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. 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.

When it is time for a cell to enter S phase, complexes of cyclin-dependent kinases (CDK) and cyclins phosphorylate pRb, inhibiting its activity. 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.

Phosphorylation of pRb allows E2F-DP to dissociate from pRb and become active. 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.

See also

• p53 - involved in the DNA repair support function of pRb
• Transcription coregulator

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.CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Multiple names: authors list (link)
• 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

• RB1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Retinoblastoma+genes at the US National Library of Medicine Medical Subject Headings (MeSH)
• Retinoblastoma Genetics
• There is a diagram of the pRb-E2F interactions here.

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