Retinoblastoma benzeri protein 2

Retinoblastoma-benzeri protein 2, insanlarda RBL2 geni tarafından kodlanan bir proteindir.Mayol X, Graña X, Baldi A, Sang N, Hu Q, Giordano A (Sep 1993). "Cloning of a new member of the retinoblastoma gene family (pRb2) which binds to the E1A transforming domain". Oncogene. 8 (9): 2561–6. PMID 8361765Baldi A, Boccia V, Claudio PP, De Luca A, Giordano A (May 1996). "Genomic structure of the human retinoblastoma-related Rb2/p130 gene". Proceedings of the National Academy of Sciences of the United States of America. 93 (10): 4629–32. Bibcode:1996PNAS...93.4629B. doi:10.1073/pnas.93.10.4629. PMC 39329. PMID 8643454. RBL2, insan genomunda kodlanan üç retinoblastoma proteininden (Rb ve RBL1 ile birlikte) biridir.

Etkileşimleri
Retinoblastoma-benzeri protein 2'nin aşağıdakilerle etkileşime girdiği gösterilmiştir:

 BRCA1Fan S, Yuan R, Ma YX, Xiong J, Meng Q, Erdos M, et al. (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
 BRF1Sutcliffe 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.
 C-RafWang S, Ghosh RN, Chellappan SP (Dec 1998). "Raf-1 physically interacts with Rb and regulates its function: a link between mitogenic signaling and cell cycle regulation". Molecular and Cellular Biology. 18 (12): 7487–98. doi:10.1128/mcb.18.12.7487. PMC 109329. PMID 9819434.
 Siklin E1Shanahan 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.Li Y, Graham C, Lacy S, Duncan AM, Whyte P (Dec 1993). "The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E". Genes & Development. 7 (12A): 2366–77. doi:10.1101/gad.7.12a.2366. PMID 8253383.
 Siklin bağımlı kinaz 2Lacy S, Whyte P (May 1997). "Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes". Oncogene. 14 (20): 2395–406. doi:10.1038/sj.onc.1201085. PMID 9188854. S2CID 26359262.
 HDAC1Ferreira 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 9724731Bouzahzah B, Fu M, Iavarone A, Factor VM, Thorgeirsson SS, Pestell RG (Aug 2000). "Transforming growth factor-beta1 recruits histone deacetylase 1 to a p130 repressor complex in transgenic mice in vivo". Cancer Research. 60 (16): 4531–7. PMID 10969803.
 ProhibitinWang 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
 RBBP8Meloni AR, Smith EJ, Nevins JR (Aug 1999). "A mechanism for Rb/p130-mediated transcription repression involving recruitment of the CtBP corepressor". Proceedings of the National Academy of Sciences of the United States of America. 96 (17): 9574–9. Bibcode:1999PNAS...96.9574M. doi:10.1073/pnas.96.17.9574. PMC 22250. PMID 10449734Fusco 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.

İnsan Hastalıkları
RBL2 genindeki mutasyonlar, morfolojik ve davranışsal anormalliklerle karakterize edilen ağır bir nörogelişimsel bozukluk ile ilişkilendirilmiştir. Bildirilen klinik bulgular arasında entelektüel yetersizlik, gelişimsel gecikme, mikrosefali, dismorfik özellikler, yürüme bozuklukları ve nöbetler yer almaktadır.Brunet T, Radivojkov-Blagojevic M, Lichtner P, Kraus V, Meitinger T, Wagner M (March 2020). "Biallelic loss-of-function variants in RBL2 in siblings with a neurodevelopmental disorder". Annals of Clinical and Translational Neurology. 7 (3): 390–396. doi:10.1002/acn3.50992. PMC 7086002. PMID 32105419.Samra N, Toubiana S, Yttervik H, Tzur-Gilat A, Morani I, Itzkovich C, et al. (November 2021). "RBL2 bi-allelic truncating variants cause severe motor and cognitive impairment without evidence for abnormalities in DNA methylation or telomeric function". Journal of Human Genetics. 66 (11): 1101–1112. doi:10.1038/s10038-021-00931-z. PMID 33980986.

RBL2 ile ilişkili hastalığın genetik temeli, her iki aleli etkileyen fonksiyon kaybı mutasyonlarına dayanmaktadır. Bu mutasyonlar arasında anlamsız (nonsense) mutasyonlar, çerçeve kayması (frameshift) mutasyonları, eklenme (splicing) mutasyonları ve delesyonlar bulunmaktadır.Aughey GN, Cali E, Maroofian R, Zaki MS, Pagnamenta AT, Ali Z, et al. (December 2024). "Clinical and genetic characterization of a progressive RBL2-associated neurodevelopmental disorder". Brain. 148 (4): 1194–1211. doi:10.1093/brain/awae363. PMC 11967543. PMID 39692517.

RBL2 ile ilişkili hastalık, nadir görülen bir genetik bozukluk olup, 2025 yılı itibarıyla dünya genelinde yalnızca 35 hasta tanımlanmıştır.

Ayrıca Bakınız
 Cep proteinleri ailesi

Kaynakça

Kategori:Transkripsiyon faktörleri