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Retinoblastoma-like protein 1

From Wikipedia, the free encyclopedia

RBL1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRBL1, CP107, PRB1, p107, retinoblastoma-like 1, RB transcriptional corepressor like 1
External IDsOMIM: 116957 MGI: 103300 HomoloGene: 2172 GeneCards: RBL1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002895
NM_183404
NM_001323281
NM_001323282

NM_001139516
NM_011249

RefSeq (protein)

NP_001310210
NP_001310211
NP_002886
NP_899662

NP_001132988
NP_035379

Location (UCSC)Chr 20: 37 – 37.1 MbChr 2: 156.99 – 157.05 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Retinoblastoma-like 1 (p107), also known as RBL1, is a protein that in humans is encoded by the RBL1 gene.[5][6]

YouTube Encyclopedic

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  • Tumor suppressors | Biomolecules | MCAT | Khan Academy
  • CDKs, cyclines, cell cycle
  • p53
  • Caspase: The (not so) Friendly Protein
  • Oncogenes & Tumor Suppressor Genes Bax P53 MYC Bcl-2 BRCA Trastuzumab Rb

Transcription

Voiceover: Tumor suppressor genes are those genes whose protein products either have a halting effect on the regulation of the cell cycle, or they can also promote apoptosis, or sometimes both. So in other words these proteins are like big stop signs that act as safety checks to help stop the mistakes in cell division that can lead to uncontrolled cell growth and cancer. Now there are several sort of categories of tumor suppressor proteins. Those that recognize DNA damage and either repair it or initiate program cell death, apoptosis if it can't be repaired, so DNA repair proteins. Then there are those proteins that act as repressors of genes that are essential for the continuation of the cell cycle. So if these genes are actively repressed, and thus not expressed, the cell cycle does not continue on. So you have cell cycle repressors. With tumor suppressors there is this concept called the "Two-Hit Hypothesis." In which both alleles, and remember that alleles are basically the copies for a certain gene. And you have two copies for any given gene. One on the chromosome you got from your mom. And one on the chromosome you got from your dad. Now in the Two-Hit Hypothesis both alleles must be mutated before the effect is manifested. Because if only one of the alleles for the gene is damaged. Then you have this, sort of backup second copy, that can still produce the protective protein. So you need two hits. One hit for each of the alleles that you have. Another way that you can think of this is that in mutated oncogenes these alleles are typically dominant. So a mutation only one of the alleles yields the cancerous phenotype. But with a mutated tumor suppressor allele these mutations are recessive. Because both alleles must be mutated in order to lead to the cancerous phenotype. The Two-Hit Hypothesis was first proposed with cases of Retinoblastoma. Rapidly developing cancer that originates from the immature cells of the retina. The light detecting tissue of your eye. And I'll write this as pRb for Retinoblastoma protein. Now the Retinoblastoma protein prevents the cell from replicating when its DNA is damaged. And it does this by preventing progression of the cell cycle from G1 into the S phase or synthesis phase. So the Retinoblastoma protein binds and inhibits transcription factors. Which normally push the cell into the S phase. And this complex acts as a growth suppressor and so the cell remains in the G1 phase. This complex also attracts a histone deacetylase protein to the chromatin. Which reduces transcription of S phase promoting factors. And you can remember this by recalling that histone deacetylase leads to chromatin condensation. Or transcriptionally inactive chromatin. So this also further suppresses DNA synthesis. Another very well known tumor suppressor protein is the p53 protein. Homozygous loss of this protein is found in up to 65% of colon cancers, 50% of lung cancers, and also in breast cancers. So this is clearly a very critical tumor suppressor protein. And so p53 activates DNA repair proteins when DNA has sustained damage. And it can also arrest growth by holding the cell cycle hostage, if you will, at the G1 to S regulation point. And this gives DNA repair proteins some time to fix the damage and allow for continuation of the cell cycle. So specifically p53 binds DNA and activates several genes including ones that code for protein called p21, whichs binds the cyclin-CDK or cyclin-dependent kinase complex, which is actually the complex responsible for pushing the cell from the G1 to S phase in the cell cycle. P53 also functions in the initiation of apoptosis if the damage to DNA is irreparable. One significant exception to the Two-Hit rule for tumor suppressor genes is with certain mutations of the p53 gene product. Which can then result in what is called a "Dominant Negative." Meaning that a mutated p53 protein can prevent the protein product of the normal allele from functioning. So don't forget to sort of keep that in the back of your mind when you're thinking about tumor suppressor genes.

Function

The protein encoded by this gene is similar in sequence and possibly function to the product of the retinoblastoma 1 (RB1) gene. The RB1 gene product is a tumor suppressor protein that appears to be involved in cell cycle regulation, as it is phosphorylated in the S to M phase transition and is dephosphorylated in the G1 phase of the cell cycle. Both the RB1 protein and the product of this gene can form a complex with adenovirus E1A protein and SV40 Large T-antigen, with the SV40 large T-antigen binding only to the unphosphorylated form of each protein. In addition, both proteins can inhibit the transcription of cell cycle genes containing E2F binding sites in their promoters. Due to the sequence and biochemical similarities with the RB1 protein, it is thought that the protein encoded by this gene may also be a tumor suppressor. Two transcript variants encoding different isoforms have been found for this gene.[5]

Interactions

Retinoblastoma-like protein 1 has been shown to interact with:

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000080839 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027641 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: RBL1 retinoblastoma-like 1 (p107)".
  6. ^ Ewen ME, Xing YG, Lawrence JB, Livingston DM (Sep 1991). "Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein". Cell. 66 (6): 1155–64. doi:10.1016/0092-8674(91)90038-Z. PMID 1833063. S2CID 27478008.
  7. ^ a b Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
  8. ^ Fan S, Yuan R, Ma YX, Xiong J, Meng Q, Erdos M, Zhao JN, Goldberg ID, Pestell RG, Rosen EM (Aug 2001). "Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding". Oncogene. 20 (35): 4827–41. doi:10.1038/sj.onc.1204666. PMID 11521194.
  9. ^ Sutcliffe JE, Cairns CA, McLees A, Allison SJ, Tosh K, White RJ (Jun 1999). "RNA polymerase III transcription factor IIIB is a target for repression by pocket proteins p107 and p130". Molecular and Cellular Biology. 19 (6): 4255–61. doi:10.1128/mcb.19.6.4255. PMC 104385. PMID 10330166.
  10. ^ a b Dyson N, Dembski M, Fattaey A, Ngwu C, Ewen M, Helin K (Dec 1993). "Analysis of p107-associated proteins: p107 associates with a form of E2F that differs from pRB-associated E2F-1". Journal of Virology. 67 (12): 7641–7. doi:10.1128/JVI.67.12.7641-7647.1993. PMC 238233. PMID 8230483.
  11. ^ a b Joaquin M, Bessa M, Saville MK, Watson RJ (Nov 2002). "B-Myb overcomes a p107-mediated cell proliferation block by interacting with an N-terminal domain of p107". Oncogene. 21 (52): 7923–32. doi:10.1038/sj.onc.1206001. PMID 12439743. S2CID 21761703.
  12. ^ Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E (Feb 1999). "Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest". Molecular and Cellular Biology. 19 (2): 1460–9. doi:10.1128/mcb.19.2.1460. PMC 116074. PMID 9891079.
  13. ^ Leng X, Noble M, Adams PD, Qin J, Harper JW (Apr 2002). "Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4". Molecular and Cellular Biology. 22 (7): 2242–54. doi:10.1128/mcb.22.7.2242-2254.2002. PMC 133692. PMID 11884610.
  14. ^ Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin WG, Seto E, Branton PE (Oct 1999). "RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins". Molecular and Cellular Biology. 19 (10): 6632–41. doi:10.1128/mcb.19.10.6632. PMC 84642. PMID 10490602.
  15. ^ Ferreira R, Magnaghi-Jaulin L, Robin P, Harel-Bellan A, Trouche D (Sep 1998). "The three members of the pocket proteins family share the ability to repress E2F activity through recruitment of a histone deacetylase". Proceedings of the National Academy of Sciences of the United States of America. 95 (18): 10493–8. Bibcode:1998PNAS...9510493F. doi:10.1073/pnas.95.18.10493. PMC 27922. PMID 9724731.
  16. ^ Joaquin M, Watson RJ (Nov 2003). "The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase inhibitory activity of p57(KIP2) by interacting with its cyclin-binding domain". The Journal of Biological Chemistry. 278 (45): 44255–64. doi:10.1074/jbc.M308953200. PMID 12947099.
  17. ^ Chen CR, Kang Y, Siegel PM, Massagué J (Jul 2002). "E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression". Cell. 110 (1): 19–32. doi:10.1016/s0092-8674(02)00801-2. PMID 12150994. S2CID 8945574.
  18. ^ Wang S, Nath N, Adlam M, Chellappan S (Jun 1999). "Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function". Oncogene. 18 (23): 3501–10. doi:10.1038/sj.onc.1202684. PMID 10376528. S2CID 33828482.
  19. ^ Fusco C, Reymond A, Zervos AS (Aug 1998). "Molecular cloning and characterization of a novel retinoblastoma-binding protein". Genomics. 51 (3): 351–8. doi:10.1006/geno.1998.5368. PMID 9721205.

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


Further reading

External links

This page was last edited on 4 January 2024, at 09:04
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