ABL (gene)

From Wikipedia, the free encyclopedia
  (Redirected from Abl gene)
Jump to: navigation, search
C-abl oncogene 1, non-receptor tyrosine kinase
Protein ABL1 PDB 1ab2.png
PDB rendering based on 1ab2.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ABL1 ; ABL; JTK7; bcr/abl; c-ABL; p150; v-abl
External IDs OMIM189980 MGI87859 HomoloGene3783 ChEMBL: 1862 GeneCards: ABL1 Gene
EC number 2.7.10.2
RNA expression pattern
PBB GE ABL1 202123 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 25 11350
Ensembl ENSG00000097007 ENSMUSG00000026842
UniProt P00519 P00520
RefSeq (mRNA) NM_005157 NM_001112703
RefSeq (protein) NP_005148 NP_001106174
Location (UCSC) Chr 9:
133.59 – 133.76 Mb
Chr 2:
31.69 – 31.8 Mb
PubMed search [1] [2]

Abelson murine leukemia viral oncogene homolog 1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL) located on chromosome 9.[1] c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene.

Function[edit]

The ABL1 proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Activity of ABL1 protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. The t(9;22) translocation results in the head-to-tail fusion of the BCR and ABL1 genes, leading to a fusion gene present in many cases of chronic myelogenous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function for ABL1. The ABL1 gene is expressed as either a 6- or a 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2-11.[2]

Clinical significance[edit]

ABL1 kinase domain (blue) in complex with the second-generation Bcr-Abl tyrosine-kinase inhibitor nilotinib (red)

Mutations in the ABL1 gene are associated with chronic myelogenous leukemia (CML). In CML, the gene is activated by being translocated within the BCR (breakpoint cluster region) gene on chromosome 22. This new fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows the cells to proliferate without being regulated by cytokines. This, in turn, allows the cell to become cancerous.

This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in chronic myelogenous leukemia (CML) and rarely in some other leukemia forms. The BCR-ABL transcript encodes a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. The BCR-ABL protein can be inhibited by various small molecules. One such inhibitor is imatinib mesylate, which occupies the tyrosine kinase domain and inhibits BCR-ABL's influence on the cell cycle. Second generation BCR-ABL tyrosine-kinase inhibitors are also under development to inhibit BCR-ABL mutants resistant to imatinib.

Interactions[edit]

Abl gene has been shown to interact with:

Regulation[edit]

There is some evidence that the expression of Abl is regulated by the microRNA miR-203.[51]

See also[edit]

References[edit]

  1. ^ Szczylik C, Skorski T, Nicolaides NC, Manzella L, Malaguarnera L, Venturelli D, Gewirtz AM, Calabretta B (August 1991). "Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides". Science 253 (5019): 562–5. doi:10.1126/science.1857987. PMID 1857987. 
  2. ^ "Entrez Gene: ABL1 v-abl Abelson murine leukemia viral oncogene homolog 1". 
  3. ^ Tani K, Sato Seiichi, Sukezane Taiko, Kojima Hiroshi, Hirose Hidenori, Hanafusa Hidesaburo, Shishido Tomoyuki (June 2003). "Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian enabled (Mena) by c-Abl kinase". J. Biol. Chem. 278 (24): 21685–92. doi:10.1074/jbc.M301447200. PMID 12672821. 
  4. ^ Biesova Z, Piccoli C, Wong W T (January 1997). "Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth". Oncogene 14 (2): 233–41. doi:10.1038/sj.onc.1200822. PMID 9010225. 
  5. ^ Yamamoto A, Suzuki T, Sakaki Y (June 2001). "Isolation of hNap1BP which interacts with human Nap1 (NCKAP1) whose expression is down-regulated in Alzheimer's disease". Gene 271 (2): 159–69. doi:10.1016/S0378-1119(01)00521-2. PMID 11418237. 
  6. ^ a b Cao C, Leng Yumei, Li Chufang, Kufe Donald (April 2003). "Functional interaction between the c-Abl and Arg protein-tyrosine kinases in the oxidative stress response". J. Biol. Chem. 278 (15): 12961–7. doi:10.1074/jbc.M300058200. PMID 12569093. 
  7. ^ Dai Z, Pendergast A M (November 1995). "Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity". Genes Dev. 9 (21): 2569–82. doi:10.1101/gad.9.21.2569. PMID 7590236. 
  8. ^ a b Chen G, Yuan S S, Liu W, Xu Y, Trujillo K, Song B, Cong F, Goff S P, Wu Y, Arlinghaus R, Baltimore D, Gasser P J, Park M S, Sung P, Lee E Y (April 1999). "Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl". J. Biol. Chem. 274 (18): 12748–52. doi:10.1074/jbc.274.18.12748. PMID 10212258. 
  9. ^ Shafman T, Khanna K K, Kedar P, Spring K, Kozlov S, Yen T, Hobson K, Gatei M, Zhang N, Watters D, Egerton M, Shiloh Y, Kharbanda S, Kufe D, Lavin M F (May 1997). "Interaction between ATM protein and c-Abl in response to DNA damage". Nature 387 (6632): 520–3. doi:10.1038/387520a0. PMID 9168117. 
  10. ^ a b Kishi S, Zhou X Z, Ziv Y, Khoo C, Hill D E, Shiloh Y, Lu K P (August 2001). "Telomeric protein Pin2/TRF1 as an important ATM target in response to double strand DNA breaks". J. Biol. Chem. 276 (31): 29282–91. doi:10.1074/jbc.M011534200. PMID 11375976. 
  11. ^ Salgia R, Pisick E, Sattler M, Li J L, Uemura N, Wong W K, Burky S A, Hirai H, Chen L B, Griffin J D (October 1996). "p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene". J. Biol. Chem. 271 (41): 25198–203. doi:10.1074/jbc.271.41.25198. PMID 8810278. 
  12. ^ Mayer BJ, Hirai H, Sakai R (March 1995). "Evidence that SH2 domains promote processive phosphorylation by protein-tyrosine kinases". Curr. Biol. 5 (3): 296–305. doi:10.1016/S0960-9822(95)00060-1. PMID 7780740. 
  13. ^ a b Puil L, Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci P G, Arlinghaus R, Pawson T (February 1994). "Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway". EMBO J. 13 (4): 764–73. PMC 394874. PMID 8112292. 
  14. ^ Ling X, Ma Guozhen, Sun Tong, Liu Jiaxin, Arlinghaus Ralph B (January 2003). "Bcr and Abl interaction: oncogenic activation of c-Abl by sequestering Bcr". Cancer Res. 63 (2): 298–303. PMID 12543778. 
  15. ^ Pendergast AM, Muller A J, Havlik M H, Maru Y, Witte O N (July 1991). "BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner". Cell 66 (1): 161–71. doi:10.1016/0092-8674(91)90148-R. PMID 1712671. 
  16. ^ Foray N, Marot Didier, Randrianarison Voahangy, Venezia Nicole Dalla, Picard Didier, Perricaudet Michel, Favaudon Vincent, Jeggo Penny (June 2002). "Constitutive Association of BRCA1 and c-Abl and Its ATM-Dependent Disruption after Irradiation". Mol. Cell. Biol. 22 (12): 4020–32. doi:10.1128/MCB.22.12.4020-4032.2002. PMC 133860. PMID 12024016. 
  17. ^ Cao C, Leng Yumei, Kufe Donald (August 2003). "Catalase activity is regulated by c-Abl and Arg in the oxidative stress response". J. Biol. Chem. 278 (32): 29667–75. doi:10.1074/jbc.M301292200. PMID 12777400. 
  18. ^ a b Miyoshi-Akiyama T, Aleman L M, Smith J M, Adler C E, Mayer B J (July 2001). "Regulation of Cbl phosphorylation by the Abl tyrosine kinase and the Nck SH2/SH3 adaptor". Oncogene 20 (30): 4058–69. doi:10.1038/sj.onc.1204528. PMID 11494134. 
  19. ^ a b Soubeyran P, Barac Ana, Szymkiewicz Iwona, Dikic Ivan (February 2003). "Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl". Biochem. J. 370 (Pt 1): 29–34. doi:10.1042/BJ20021539. PMC 1223168. PMID 12475393. 
  20. ^ a b c Ren R, Ye Z S, Baltimore D (April 1994). "Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding sites". Genes Dev. 8 (7): 783–95. doi:10.1101/gad.8.7.783. PMID 7926767. 
  21. ^ Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, Druker B J (January 1997). "Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation". Blood 89 (1): 297–306. PMID 8978305. 
  22. ^ Kyono WT, de Jong R, Park R K, Liu Y, Heisterkamp N, Groffen J, Durden D L (November 1998). "Differential interaction of Crkl with Cbl or C3G, Hef-1, and gamma subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (Fc gamma RI)". J. Immunol. 161 (10): 5555–63. PMID 9820532. 
  23. ^ van Dijk TB, van Den Akker E, Amelsvoort M P, Mano H, Löwenberg B, von Lindern M (November 2000). "Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells". Blood 96 (10): 3406–13. PMID 11071635. 
  24. ^ Yamanashi Y, Baltimore D (January 1997). "Identification of the Abl- and rasGAP-associated 62 kDa protein as a docking protein, Dok". Cell 88 (2): 205–11. doi:10.1016/S0092-8674(00)81841-3. PMID 9008161. 
  25. ^ Yu HH, Zisch A H, Dodelet V C, Pasquale E B (July 2001). "Multiple signaling interactions of Abl and Arg kinases with the EphB2 receptor". Oncogene 20 (30): 3995–4006. doi:10.1038/sj.onc.1204524. PMID 11494128. 
  26. ^ Cao C, Leng Yumei, Huang Wei, Liu Xuan, Kufe Donald (October 2003). "Glutathione peroxidase 1 is regulated by the c-Abl and Arg tyrosine kinases". J. Biol. Chem. 278 (41): 39609–14. doi:10.1074/jbc.M305770200. PMID 12893824. 
  27. ^ Bai RY, Jahn T, Schrem S, Munzert G, Weidner K M, Wang J Y, Duyster J (August 1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene 17 (8): 941–8. doi:10.1038/sj.onc.1202024. PMID 9747873. 
  28. ^ Frantz JD, Giorgetti-Peraldi S, Ottinger E A, Shoelson S E (January 1997). "Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains". J. Biol. Chem. 272 (5): 2659–67. doi:10.1074/jbc.272.5.2659. PMID 9006901. 
  29. ^ Kumar V, Sabatini D, Pandey P, Gingras A C, Majumder P K, Kumar M, Yuan Z M, Carmichael G, Weichselbaum R, Sonenberg N, Kufe D, Kharbanda S (April 2000). "Regulation of the rapamycin and FKBP-target 1/mammalian target of rapamycin and cap-dependent initiation of translation by the c-Abl protein-tyrosine kinase". J. Biol. Chem. 275 (15): 10779–87. doi:10.1074/jbc.275.15.10779. PMID 10753870. 
  30. ^ Warmuth M, Bergmann M, Priess A, Häuslmann K, Emmerich B, Hallek M (December 1997). "The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr". J. Biol. Chem. 272 (52): 33260–70. doi:10.1074/jbc.272.52.33260. PMID 9407116. 
  31. ^ Goldberg Z, Vogt Sionov Ronit, Berger Michael, Zwang Yaara, Perets Ruth, Van Etten Richard A, Oren Moshe, Taya Yoichi, Haupt Ygal (July 2002). "Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation". EMBO J. 21 (14): 3715–27. doi:10.1093/emboj/cdf384. PMC 125401. PMID 12110584. 
  32. ^ Minegishi M, Tachibana K, Sato T, Iwata S, Nojima Y, Morimoto C (October 1996). "Structure and function of Cas-L, a 105-kD Crk-associated substrate- related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes". J. Exp. Med. 184 (4): 1365–75. doi:10.1084/jem.184.4.1365. PMC 2192828. PMID 8879209. 
  33. ^ Law SF, Estojak J, Wang B, Mysliwiec T, Kruh G, Golemis E A (July 1996). "Human enhancer of filamentation 1, a novel p130cas-like docking protein, associates with focal adhesion kinase and induces pseudohyphal growth in Saccharomyces cerevisiae". Mol. Cell. Biol. 16 (7): 3327–37. PMC 231327. PMID 8668148. 
  34. ^ Koch A, Mancini A, Stefan M, Niedenthal R, Niemann H, Tamura T (March 2000). "Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop". FEBS Lett. 469 (1): 72–6. doi:10.1016/S0014-5793(00)01242-4. PMID 10708759. 
  35. ^ Yano H, Cong F, Birge R B, Goff S P, Chao M V (February 2000). "Association of the Abl tyrosine kinase with the Trk nerve growth factor receptor". J. Neurosci. Res. 59 (3): 356–64. doi:10.1002/(SICI)1097-4547(20000201)59:3<356::AID-JNR9>3.0.CO;2-G. PMID 10679771. 
  36. ^ Yuan ZM, Shioya H, Ishiko T, Sun X, Gu J, Huang Y Y, Lu H, Kharbanda S, Weichselbaum R, Kufe D (June 1999). "p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage". Nature 399 (6738): 814–7. doi:10.1038/21704. PMID 10391251. 
  37. ^ Agami R, Blandino G, Oren M, Shaul Y (June 1999). "Interaction of c-Abl and p73alpha and their collaboration to induce apoptosis". Nature 399 (6738): 809–13. doi:10.1038/21697. PMID 10391250. 
  38. ^ Wen ST, Van Etten R A (October 1997). "The PAG gene product, a stress-induced protein with antioxidant properties, is an Abl SH3-binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity". Genes Dev. 11 (19): 2456–67. doi:10.1101/gad.11.19.2456. PMC 316562. PMID 9334312. 
  39. ^ Roig J, Tuazon P T, Zipfel P A, Pendergast A M, Traugh J A (December 2000). "Functional interaction between c-Abl and the p21-activated protein kinase γ-PAK". PNAS 97 (26): 14346–51. doi:10.1073/pnas.97.26.14346. PMC 18921. PMID 11121037. 
  40. ^ Cong F, Spencer S, Côté J F, Wu Y, Tremblay M L, Lasky L A, Goff S P (December 2000). "Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation". Mol. Cell 6 (6): 1413–23. doi:10.1016/S1097-2765(00)00138-6. PMID 11163214. 
  41. ^ Yoshida K, Komatsu Kiyoshi, Wang Hong-Gang, Kufe Donald (May 2002). "c-Abl Tyrosine Kinase Regulates the Human Rad9 Checkpoint Protein in Response to DNA Damage". Mol. Cell. Biol. 22 (10): 3292–300. doi:10.1128/MCB.22.10.3292-3300.2002. PMC 133797. PMID 11971963. 
  42. ^ Miyamura T, Nishimura J, Yufu Y, Nawata H (February 1997). "Interaction of BCR-ABL with the retinoblastoma protein in Philadelphia chromosome-positive cell lines". Int. J. Hematol. 65 (2): 115–21. doi:10.1016/S0925-5710(96)00539-7. PMID 9071815. 
  43. ^ Welch PJ, Wang J Y (November 1993). "A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle". Cell 75 (4): 779–90. doi:10.1016/0092-8674(93)90497-E. PMID 8242749. 
  44. ^ Agami R, Shaul Y (April 1998). "The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction with RFXI, a protein that binds the enhancers of several viruses and cell-cycle regulated genes". Oncogene 16 (14): 1779–88. doi:10.1038/sj.onc.1201708. PMID 9583676. 
  45. ^ Zhu J, Shore S K (December 1996). "c-ABL tyrosine kinase activity is regulated by association with a novel SH3-domain-binding protein". Mol. Cell. Biol. 16 (12): 7054–62. PMC 231708. PMID 8943360. 
  46. ^ Wisniewski D, Strife A, Swendeman S, Erdjument-Bromage H, Geromanos S, Kavanaugh W M, Tempst P, Clarkson B (April 1999). "A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP2) is constitutively tyrosine phosphorylated and associated with src homologous and collagen gene (SHC) in chronic myelogenous leukemia progenitor cells". Blood 93 (8): 2707–20. PMID 10194451. 
  47. ^ Wang B, Golemis E A, Kruh G D (July 1997). "ArgBP2, a multiple Src homology 3 domain-containing, Arg/Abl-interacting protein, is phosphorylated in v-Abl-transformed cells and localized in stress fibers and cardiocyte Z-disks". J. Biol. Chem. 272 (28): 17542–50. doi:10.1074/jbc.272.28.17542. PMID 9211900. 
  48. ^ a b Ziemnicka-Kotula D, Xu J, Gu H, Potempska A, Kim K S, Jenkins E C, Trenkner E, Kotula L (May 1998). "Identification of a candidate human spectrin Src homology 3 domain-binding protein suggests a general mechanism of association of tyrosine kinases with the spectrin-based membrane skeleton". J. Biol. Chem. 273 (22): 13681–92. doi:10.1074/jbc.273.22.13681. PMID 9593709. 
  49. ^ Bassermann F, Jahn Thomas, Miething Cornelius, Seipel Petra, Bai Ren-Yuan, Coutinho Sunita, Tybulewicz Victor L, Peschel Christian, Duyster Justus (April 2002). "Association of Bcr-Abl with the proto-oncogene Vav is implicated in activation of the Rac-1 pathway". J. Biol. Chem. 277 (14): 12437–45. doi:10.1074/jbc.M112397200. PMID 11790798. 
  50. ^ Rafalska I, Zhang Zhaiyi, Benderska Natalya, Wolff Horst, Hartmann Annette M, Brack-Werner Ruth, Stamm Stefan (August 2004). "The intranuclear localization and function of YT521-B is regulated by tyrosine phosphorylation". Hum. Mol. Genet. 13 (15): 1535–49. doi:10.1093/hmg/ddh167. PMID 15175272. 
  51. ^ Bueno MJ, Pérez de Castro I, Gómez de Cedrón M, Santos J, Calin GA, Cigudosa JC, Croce CM, Fernández-Piqueras J, Malumbres M (June 2008). "Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression". Cancer Cell 13 (6): 496–506. doi:10.1016/j.ccr.2008.04.018. PMID 18538733. 

Further reading[edit]

External links[edit]