Retinoblastoma-like protein 1 explained

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

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.^[2]

Interactions

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

• BEGAIN,
• BRCA1,^[3]
• BRF1,^[4]
• Cyclin A2,^[5]
• Cyclin-dependent kinase 2,^{[6] [7]}
• E2F1,^[8]
• HDAC1,^{[9] [10]}
• MYBL2^{[5] [11]}
• Mothers against decapentaplegic homolog 3,^[12]
• Prohibitin,^[13] and
• RBBP8.^{[14] [15]}

See also

• Pocket protein family

Further reading

• Faha B, Ewen ME, Tsai LH, Livingston DM, Harlow E . Interaction between human cyclin A and adenovirus E1A-associated p107 protein . Science . 255 . 5040 . 87–90 . Jan 1992 . 1532458 . 10.1126/science.1532458 . 1992Sci...255...87F .
• Ewen ME, Xing YG, Lawrence JB, Livingston DM . Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein . Cell . 66 . 6 . 1155–64 . Sep 1991 . 1833063 . 10.1016/0092-8674(91)90038-Z . 27478008 .
• Datta PK, Raychaudhuri P, Bagchi S . Association of p107 with Sp1: genetically separable regions of p107 are involved in regulation of E2F- and Sp1-dependent transcription . Molecular and Cellular Biology . 15 . 10 . 5444–52 . Oct 1995 . 7565695 . 230794 . 10.1128/mcb.15.10.5444.
• Zhu L, Zhu L, Xie E, Chang LS . Differential roles of two tandem E2F sites in repression of the human p107 promoter by retinoblastoma and p107 proteins . Molecular and Cellular Biology . 15 . 7 . 3552–62 . Jul 1995 . 7791762 . 230592 . 10.1128/mcb.15.7.3552.
• Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A, Weinberg RA . E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle . Proceedings of the National Academy of Sciences of the United States of America . 92 . 6 . 2403–7 . Mar 1995 . 7892279 . 42492 . 10.1073/pnas.92.6.2403 . 1995PNAS...92.2403S . free .
• Kim YW, Otterson GA, Kratzke RA, Coxon AB, Kaye FJ . Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein . Molecular and Cellular Biology . 14 . 11 . 7256–64 . Nov 1994 . 7935440 . 359260 . 10.1128/mcb.14.11.7256.
• Ginsberg D, Vairo G, Chittenden T, Xiao ZX, Xu G, Wydner KL, DeCaprio JA, Lawrence JB, Livingston DM . E2F-4, a new member of the E2F transcription factor family, interacts with p107 . Genes & Development . 8 . 22 . 2665–79 . Nov 1994 . 7958924 . 10.1101/gad.8.22.2665 . free .
• Beijersbergen RL, Kerkhoven RM, Zhu L, Carlée L, Voorhoeve PM, Bernards R . E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo . Genes & Development . 8 . 22 . 2680–90 . Nov 1994 . 7958925 . 10.1101/gad.8.22.2680 . free .
• Beijersbergen RL, Hijmans EM, Zhu L, Bernards R . Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation . The EMBO Journal . 13 . 17 . 4080–6 . Sep 1994 . 8076603 . 395329 . 10.1002/j.1460-2075.1994.tb06725.x.
• Dyson N, Dembski M, Fattaey A, Ngwu C, Ewen M, Helin K . 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 . Dec 1993 . 8230483 . 238233 . 10.1128/JVI.67.12.7641-7647.1993.
• Zhu L, van den Heuvel S, Helin K, Fattaey A, Ewen M, Livingston D, Dyson N, Harlow E . Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein . Genes & Development . 7 . 7A . 1111–25 . Jul 1993 . 8319904 . 10.1101/gad.7.7a.1111 . free .
• Ikeda MA, Jakoi L, Nevins JR . A unique role for the Rb protein in controlling E2F accumulation during cell growth and differentiation . Proceedings of the National Academy of Sciences of the United States of America . 93 . 8 . 3215–20 . Apr 1996 . 8622916 . 39585 . 10.1073/pnas.93.8.3215 . 1996PNAS...93.3215I . free .
• Xiao ZX, Ginsberg D, Ewen M, Livingston DM . Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases . Proceedings of the National Academy of Sciences of the United States of America . 93 . 10 . 4633–7 . May 1996 . 8643455 . 39330 . 10.1073/pnas.93.10.4633 . 1996PNAS...93.4633X . free .
• Vidal M, Brachmann RK, Fattaey A, Harlow E, Boeke JD . Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions . Proceedings of the National Academy of Sciences of the United States of America . 93 . 19 . 10315–20 . Sep 1996 . 8816797 . 38381 . 10.1073/pnas.93.19.10315 . 1996PNAS...9310315V . free .
• Shao Z, Siegert JL, Ruppert S, Robbins PD . Rb interacts with TAF(II)250/TFIID through multiple domains . Oncogene . 15 . 4 . 385–92 . Jul 1997 . 9242374 . 10.1038/sj.onc.1201204 . free .
• Verona R, Moberg K, Estes S, Starz M, Vernon JP, Lees JA . E2F activity is regulated by cell cycle-dependent changes in subcellular localization . Molecular and Cellular Biology . 17 . 12 . 7268–82 . Dec 1997 . 9372959 . 232584 . 10.1128/mcb.17.12.7268.
• Trimarchi JM, Fairchild B, Verona R, Moberg K, Andon N, Lees JA . E2F-6, a member of the E2F family that can behave as a transcriptional repressor . Proceedings of the National Academy of Sciences of the United States of America . 95 . 6 . 2850–5 . Mar 1998 . 9501179 . 19658 . 10.1073/pnas.95.6.2850 . 1998PNAS...95.2850T . free .
• Sterner JM, Dew-Knight S, Musahl C, Kornbluth S, Horowitz JM . Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7 . Molecular and Cellular Biology . 18 . 5 . 2748–57 . May 1998 . 9566894 . 110654 . 10.1128/mcb.18.5.2748.
• Woitach JT, Zhang M, Niu CH, Thorgeirsson SS . A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability . Nature Genetics . 19 . 4 . 371–4 . Aug 1998 . 9697699 . 10.1038/1258 . 11374970 .
• Veal E, Eisenstein M, Tseng ZH, Gill G . A cellular repressor of E1A-stimulated genes that inhibits activation by E2F . Molecular and Cellular Biology . 18 . 9 . 5032–41 . Sep 1998 . 9710587 . 109088 . 10.1128/mcb.18.9.5032.

Notes and References

1. Ewen ME, Xing YG, Lawrence JB, Livingston DM . Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein . Cell . 66 . 6 . 1155–64 . Sep 1991 . 1833063 . 10.1016/0092-8674(91)90038-Z . 27478008 .
2. Web site: Entrez Gene: RBL1 retinoblastoma-like 1 (p107).
3. Fan S, Yuan R, Ma YX, Xiong J, Meng Q, Erdos M, Zhao JN, Goldberg ID, Pestell RG, Rosen EM . Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding . Oncogene . 20 . 35 . 4827–41 . Aug 2001 . 11521194 . 10.1038/sj.onc.1204666 . free .
4. Sutcliffe JE, Cairns CA, McLees A, Allison SJ, Tosh K, White RJ . 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 . Jun 1999 . 10330166 . 104385 . 10.1128/mcb.19.6.4255.
5. Joaquin M, Bessa M, Saville MK, Watson RJ . B-Myb overcomes a p107-mediated cell proliferation block by interacting with an N-terminal domain of p107 . Oncogene . 21 . 52 . 7923–32 . Nov 2002 . 12439743 . 10.1038/sj.onc.1206001 . 21761703 .
6. Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E . 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 . Feb 1999 . 9891079 . 116074 . 10.1128/mcb.19.2.1460.
7. Leng X, Noble M, Adams PD, Qin J, Harper JW . Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4 . Molecular and Cellular Biology . 22 . 7 . 2242–54 . Apr 2002 . 11884610 . 133692 . 10.1128/mcb.22.7.2242-2254.2002.
8. Dyson N, Dembski M, Fattaey A, Ngwu C, Ewen M, Helin K . 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 . Dec 1993 . 8230483 . 238233 . 10.1128/JVI.67.12.7641-7647.1993.
9. Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin WG, Seto E, Branton PE . RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins . Molecular and Cellular Biology . 19 . 10 . 6632–41 . Oct 1999 . 10490602 . 84642 . 10.1128/mcb.19.10.6632.
10. Ferreira R, Magnaghi-Jaulin L, Robin P, Harel-Bellan A, Trouche D . 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 . Sep 1998 . 9724731 . 27922 . 10.1073/pnas.95.18.10493. 1998PNAS...9510493F . free .
11. Joaquin M, Watson RJ . 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 . Nov 2003 . 12947099 . 10.1074/jbc.M308953200 . free .
12. Chen CR, Kang Y, Siegel PM, Massagué J . E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression . Cell . 110 . 1 . 19–32 . Jul 2002 . 12150994 . 10.1016/s0092-8674(02)00801-2. 8945574 . free .
13. Wang S, Nath N, Adlam M, Chellappan S . Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function . Oncogene . 18 . 23 . 3501–10 . Jun 1999 . 10376528 . 10.1038/sj.onc.1202684 . 33828482 .
14. Fusco C, Reymond A, Zervos AS . Molecular cloning and characterization of a novel retinoblastoma-binding protein . Genomics . 51 . 3 . 351–8 . Aug 1998 . 9721205 . 10.1006/geno.1998.5368 .
15. 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 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .