oncogene proteins v abl


Summary: Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.

Top Publications

  1. Muljo S, Schlissel M. A small molecule Abl kinase inhibitor induces differentiation of Abelson virus-transformed pre-B cell lines. Nat Immunol. 2003;4:31-7 pubmed
    ..This suggests a key role for these factors, and perhaps for c-Abl itself, in the regulated activation of Ig light chain gene rearrangement...
  2. Chen Y, Rosenberg N. Lymphoid cells transformed by Abelson virus require the v-abl protein-tyrosine kinase only during early G1. Proc Natl Acad Sci U S A. 1992;89:6683-7 pubmed
  3. Kharas M, Yusuf I, Scarfone V, Yang V, Segre J, Huettner C, et al. KLF4 suppresses transformation of pre-B cells by ABL oncogenes. Blood. 2007;109:747-55 pubmed
    ..Collectively, our work identifies KLF4 as a putative tumor suppressor in B-cell malignancies. ..
  4. Zhou V, Gao X, Han S, Brinker A, Caldwell J, Gu X. An intracellular conformational sensor assay for Abl T315I. Anal Biochem. 2009;385:300-8 pubmed publisher
    ..We expect that the split luciferase-based conformational sensor approach might be more broadly useful to probe the intracellular activation of other kinases and enzymes in general. ..
  5. Kirchner D, Duyster J, Ottmann O, Schmid R, Bergmann L, Munzert G. Mechanisms of Bcr-Abl-mediated NF-kappaB/Rel activation. Exp Hematol. 2003;31:504-11 pubmed
    ..In addition, NF-kappaB/Rel activation was dependent on Ras activity. Primary CML blasts showed constitutive p65/RelA NF-kappaB/Rel DNA binding activity. Thus NF-kappaB/Rel represents a potential target for molecular therapies in CML. ..
  6. Cwynarski K, Laylor R, Macchiarulo E, Goldman J, Lombardi G, Melo J, et al. Imatinib inhibits the activation and proliferation of normal T lymphocytes in vitro. Leukemia. 2004;18:1332-9 pubmed
    ..Thus, imatinib inhibits T-cell proliferation in vitro, an effect that is APC-independent, reversible, and does not involve apoptosis induction. ..
  7. Hofmann W, Komor M, Hoelzer D, Ottmann O. Mechanisms of resistance to STI571 (Imatinib) in Philadelphia-chromosome positive acute lymphoblastic leukemia. Leuk Lymphoma. 2004;45:655-60 pubmed
    ..This may result in the proliferation of Ph + leukemic cells even in the presence of STI571. ..
  8. Courtneidge S. Cancer: Escape from inhibition. Nature. 2003;422:827-8 pubmed
  9. Evans C, Owen Lynch P, Whetton A, Dive C. Activation of the Abelson tyrosine kinase activity is associated with suppression of apoptosis in hemopoietic cells. Cancer Res. 1993;53:1735-8 pubmed
    ..DP cells died via apoptosis. At the permissive temperature ABL tyrosine kinase activity promoted IC.DP cell survival but not proliferation. ABL therefore can specifically suppress apoptosis. ..

More Information


  1. Toyofuku T, Zhang H, Kumanogoh A, Takegahara N, Yabuki M, Harada K, et al. Guidance of myocardial patterning in cardiac development by Sema6D reverse signalling. Nat Cell Biol. 2004;6:1204-11 pubmed
    ..Thus, Sema6D coordinates both compact-layer expansion and trabeculation, functioning as both a ligand and a receptor for Plexin-A1. ..
  2. Oki S, Limnander A, Yao P, Niki M, Pandolfi P, Rothman P. Dok1 and SHIP act as negative regulators of v-Abl-induced pre-B cell transformation, proliferation and Ras/Erk activation. Cell Cycle. 2005;4:310-4 pubmed
    ..These data indicate that both SHIP and Dok1 functionally regulate the activation of Ras-Erk pathway by v-Abl and affect the mitogenic activity of v-Abl transformed bone marrow cells. ..
  3. Rottapel R, Ilangumaran S, Neale C, La Rose J, Ho J, Nguyen M, et al. The tumor suppressor activity of SOCS-1. Oncogene. 2002;21:4351-62 pubmed
    ..These data suggest that loss-of-function of SOCS-1 may collaborate with a variety of hematopoietic oncogenes to facilitate tumor progression. ..
  4. Mainville C, Parmar K, Unnikrishnan I, Gong L, Raffel G, Rosenberg N. Temperature-sensitive transformation by an Abelson virus mutant encoding an altered SH2 domain. J Virol. 2001;75:1816-23 pubmed
    ..These data suggest that alteration of the FLVRES pocket affects the ability of v-Abl to interact with at least some of its substrates in a temperature-dependent fashion and identify a novel type of temperature-sensitive Abelson virus. ..
  5. Apostolidou E, Swords R, Alvarado Y, Giles F. Treatment of acute lymphoblastic leukaemia : a new era. Drugs. 2007;67:2153-71 pubmed
  6. Arteaga C, Baselga J. Tyrosine kinase inhibitors: why does the current process of clinical development not apply to them?. Cancer Cell. 2004;5:525-31 pubmed
  7. Warren D, Heilpern A, Berg K, Rosenberg N. The carboxyl terminus of v-Abl protein can augment SH2 domain function. J Virol. 2000;74:4495-504 pubmed
  8. Sun J, Zhang X, He Z, Gu Y, Yu Y, Fang Y, et al. [The mechanism of apoptosis of chronic myeloid leukemia cells induced by the novel p210 bcr/abl inhibitor berbamine]. Zhonghua Yi Xue Za Zhi. 2006;86:2246-51 pubmed
  9. Cohen L, Mohr R, Chen Y, Huang M, Kato R, Dorin D, et al. Transcriptional activation of a ras-like gene (kir) by oncogenic tyrosine kinases. Proc Natl Acad Sci U S A. 1994;91:12448-52 pubmed
    ..BCR/ABL and v-Abl induce transcription of the kir gene via specific signaling pathway(s), but kir overexpression alone is not sufficient to mediate transformation. ..
  10. Helmink B, Bredemeyer A, Lee B, Huang C, Sharma G, Walker L, et al. MRN complex function in the repair of chromosomal Rag-mediated DNA double-strand breaks. J Exp Med. 2009;206:669-79 pubmed publisher
  11. Stoklosa T, Slupianek A, Datta M, Nieborowska Skorska M, Nowicki M, Koptyra M, et al. BCR/ABL recruits p53 tumor suppressor protein to induce drug resistance. Cell Cycle. 2004;3:1463-72 pubmed
    ..In conclusion, accumulation of the p53 protein contributed to prolonged G(2)/M checkpoint activation and drug resistance in myeloid cells expressing the BCR/ABL oncoproteins. ..
  12. Gong L, Unnikrishnan I, Raghavan A, Parmar K, Rosenberg N. Active Akt and functional p53 modulate apoptosis in Abelson virus-transformed pre-B cells. J Virol. 2004;78:1636-44 pubmed
    ..These data indicate that an intact Src homology 2 (SH2) domain is not critical for apoptosis suppression and suggest that signals transmitted through Akt and p53 play an important role in the response. ..
  13. Gertler F, Hill K, Clark M, Hoffmann F. Dosage-sensitive modifiers of Drosophila abl tyrosine kinase function: prospero, a regulator of axonal outgrowth, and disabled, a novel tyrosine kinase substrate. Genes Dev. 1993;7:441-53 pubmed
    ..The disabled protein is colocalized with abl in axons, its predicted amino acid sequence contains 10 motifs similar to the major autophosphorylation site of abl, and the protein is recognized by antibodies to phosphotyrosine. ..
  14. Parmar K, Rosenberg N. Ras complements the carboxyl terminus of v-Abl protein in lymphoid transformation. J Virol. 1996;70:1009-15 pubmed
    ..Signals transmitted via this connection may enhance those mediated via other regions of the v-Abl protein and facilitate transformation of primary, nonimmortalized cells such as pre-B lymphocytes...
  15. Cong F, Yuan B, Goff S. Characterization of a novel member of the DOK family that binds and modulates Abl signaling. Mol Cell Biol. 1999;19:8314-25 pubmed
    ..The inhibitory effect requires the PTB domain of DOKL. Finally, overexpression of DOKL in NIH 3T3 cells inhibits the transforming activity of v-Abl. These results suggest that DOKL may modulate Abl function. ..
  16. Danial N, Losman J, Lu T, Yip N, Krishnan K, Krolewski J, et al. Direct interaction of Jak1 and v-Abl is required for v-Abl-induced activation of STATs and proliferation. Mol Cell Biol. 1998;18:6795-804 pubmed
    ..We propose that Jak1 is a mediator of v-Abl-induced STAT activation and v-Abl induced proliferation in BAF/3 cells, and may be important for efficient transformation of immature B cells by the v-abl oncogene. ..
  17. Lindauer M, Hochhaus A. Dasatinib. Recent Results Cancer Res. 2010;184:83-102 pubmed publisher
    ..Side effects of dasatinib are frequent but mostly moderate and manageable and include cytopenias and pleural effusions. The role of dasatinib in other diseases, including solid tumors, has to be identified. ..
  18. Qin X, Reichlin A, Luo Y, Roeder R, Nussenzweig M. OCA-B integrates B cell antigen receptor-, CD40L- and IL 4-mediated signals for the germinal center pathway of B cell development. EMBO J. 1998;17:5066-75 pubmed
    ..Thus, OCA-B is the first example of a transcriptional coactivator that is both synergistically induced by and required for integration of signals that mediate cell fate decisions. ..
  19. Wang L, Pan Q, Fu J, Shi J, Jin J, Li J, et al. FIP1L1-PDGFRalpha alone or with other genetic abnormalities reveals disease progression in chronic eosinophilic leukemia but good response to imatinib. Chin Med J (Engl). 2008;121:867-73 pubmed
    ..It reflects the disease progression and there is a good response to imatinib. Detection of the FIP1L1-PDGFRalpha fusion gene is valid for both CEL diagnosis and therapy surveillance. ..
  20. Kapeller R, Moriarty A, Strauss A, Stubdal H, Theriault K, Siebert E, et al. Tyrosine phosphorylation of tub and its association with Src homology 2 domain-containing proteins implicate tub in intracellular signaling by insulin. J Biol Chem. 1999;274:24980-6 pubmed
    ..These data suggest that Tub may function as an adaptor protein linking the insulin receptor, and possibly other protein-tyrosine kinases, to SH2-containing proteins. ..
  21. Coutinho S, Jahn T, Lewitzky M, Feller S, Hutzler P, Peschel C, et al. Characterization of Ggrb4, an adapter protein interacting with Bcr-Abl. Blood. 2000;96:618-24 pubmed
    ..Grb4 may therefore play a role in the molecular pathogenesis of chronic myelogenous leukemia. (Blood. 2000;96:618-624) (Blood. 2000;96:618-624) ..
  22. Allen P, Morgan G, Wiedemann L. Philadelphia chromosome-positive leukaemia: the translocated genes and their gene products. Baillieres Clin Haematol. 1992;5:897-930 pubmed
    ..In spite of this, our understanding of the molecular details of these chromosomal translocations allows the design of therapies directed against their unique, leukaemia-specific proteins and RNA products. ..
  23. Wen S, Van Etten R. 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. 1997;11:2456-67 pubmed
    ..When transfected in NIH-3T3 cells, Pag is localized to nucleus and cytoplasm and rescues the cytostatic effect induced by c-Abl. These observations suggest Pag is a physiological inhibitor of c-Abl in vivo. ..
  24. Oki S, Limnander A, Danial N, Rothman P. Functional involvement of Akt signaling downstream of Jak1 in v-Abl-induced activation of hematopoietic cells. Blood. 2002;100:966-73 pubmed
    ..These results suggest that Jak1-dependent Akt activation is important in v-Abl-mediated transformation. ..
  25. Shore S, Tantravahi R, Reddy E. Transforming pathways activated by the v-Abl tyrosine kinase. Oncogene. 2002;21:8568-76 pubmed
    ..Finally, we discuss the mechanisms associated with v-Abl mediated transformation through examination of the various signal transduction pathways activated by this oncogene. ..
  26. Lee H, Gaughan J, Tsygankov A. c-Cbl facilitates cytoskeletal effects in v-Abl transformed fibroblast through Rac1- and Rap1-mediated signaling. Int J Biochem Cell Biol. 2008;40:1930-43 pubmed publisher
    ..Overall, our findings are consistent with the model describing the connection of c-Cbl to the cytoskeletal rearrangements via two pathways, one of which is mediated by PI3K and Rac1, and the other, by CrkL/C3G, Rap1 and Rac1. ..
  27. Maruoka M, Suzuki J, Kawata S, Yoshida K, Hirao N, Sato S, et al. Identification of B cell adaptor for PI3-kinase (BCAP) as an Abl interactor 1-regulated substrate of Abl kinases. FEBS Lett. 2005;579:2986-90 pubmed
    ..These results show that Abi-1 promotes Abl-mediated BCAP phosphorylation and suggest that Abi-1 in general coordinates kinase-substrate interactions. ..
  28. Mayorga M, Sanchis D, Perez de Santos A, Velasco A, Dolcet X, Casanova J, et al. Antiproliferative effect of STI571 on cultured human cutaneous melanoma-derived cell lines. Melanoma Res. 2006;16:127-35 pubmed
    ..The identification of the target of STI571 in human cutaneous melanoma cells would allow the selection of patients who could benefit from this treatment. ..
  29. Swimm A, Bornmann W, Jiang M, Imperiale M, Lukacher A, Kalman D. Abl family tyrosine kinases regulate sialylated ganglioside receptors for polyomavirus. J Virol. 2010;84:4243-51 pubmed publisher
    ..Thus, Abl family kinases regulate the susceptibility of cells to polyomavirus infection by modulating gangliosides required for viral attachment. ..
  30. Sudo H, Maru Y. LAPSER1 is a putative cytokinetic tumor suppressor that shows the same centrosome and midbody subcellular localization pattern as p80 katanin. FASEB J. 2007;21:2086-100 pubmed
    ..These results suggest that LAPSER1 participates in cytokinesis by interacting with p80 katanin, the disruption of which may potentially cause genetic instability and cancer. ..
  31. Weissinger E, Eissner G, Grammer C, Fackler S, Haefner B, Yoon L, et al. Inhibition of the Raf-1 kinase by cyclic AMP agonists causes apoptosis of v-abl-transformed cells. Mol Cell Biol. 1997;17:3229-41 pubmed
  32. Tsuchiya K, Kawano Y, Kojima T, Nagata K, Takao T, Okada M, et al. Molecular cloning and characterization of TPP36 and its isoform TPP32, novel substrates of Abl tyrosine kinase. FEBS Lett. 2003;537:203-9 pubmed
    ..Thus, TPP36/32 appear to be novel substrates of Abl tyrosine kinase. ..
  33. Banerjee A, Rothman P. IL-7 reconstitutes multiple aspects of v-Abl-mediated signaling. J Immunol. 1998;161:4611-7 pubmed
    ..These results identify a potential role for IL-7 signaling pathways in transformation by v-Abl while demonstrating that a combination of IL-4 and IL-7 signaling cannot substitute for an active v-Abl kinase in transformed pre-B cells...
  34. Zou X, Cong F, Coutts M, Cattoretti G, Goff S, Calame K. p53 deficiency increases transformation by v-Abl and rescues the ability of a C-terminally truncated v-Abl mutant to induce pre-B lymphoma in vivo. Mol Cell Biol. 2000;20:628-33 pubmed
  35. Westphal R, Soderling S, Alto N, Langeberg L, Scott J. Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold. EMBO J. 2000;19:4589-600 pubmed
    ..Thus, we propose a previously unrecognized function for WAVE-1 as an actin-associated scaffolding protein that recruits PKA and Abl. ..
  36. Sattler M, Verma S, Pride Y, Salgia R, Rohrschneider L, Griffin J. SHIP1, an SH2 domain containing polyinositol-5-phosphatase, regulates migration through two critical tyrosine residues and forms a novel signaling complex with DOK1 and CRKL. J Biol Chem. 2001;276:2451-8 pubmed
    ..Overall, these data suggest that proteins that interact with SHIP1 through Tyr(917) and Tyr(1020), such as DOK1 and SHC, are likely to be involved in the regulation of SHIP1 dependent migration. ..
  37. Mukundan C, Gurish M, Austen K, Hechtman H, Friend D. The presence of v-abl-transformed V3 mast cells in the lungs augments pulmonary vascular permeability to acid aspiration. J Histochem Cytochem. 2001;49:793-4 pubmed
    ..By increasing pulmonary mast cells through adoptive transfer of v-abl-transformed mast cells (V3MCs) into BALB/c mice, we now show that the greater mast cell number in the lung is associated with increased pulmonary injury. ..
  38. Antczak C, Veach D, Ramirez C, Minchenko M, Shum D, Calder P, et al. Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. Bioorg Med Chem Lett. 2009;19:6872-6 pubmed publisher
    ..Altogether, our results provide an insight into the SAR of pyrido[2,3-d]pyrimidin-7-ones for the development of drug candidates with improved potency and selectivity for the targeted treatment of CML. ..
  39. Oka T, Yutsudo M, Inoue H, Higuchi F, Hakura A. Characterization of flat revertants isolated from cells transformed by Abelson murine leukemia virus (Ab-MuLV). J Cell Physiol. 1990;145:428-33 pubmed
    ..These findings suggest the existence of a specific mechanism(s) for elimination of the v-abl oncogene by segregation, mutation, or gene rearrangement in these cells. ..
  40. Carter T, Wodicka L, Shah N, Velasco A, Fabian M, Treiber D, et al. Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci U S A. 2005;102:11011-6 pubmed
  41. Nunoda K, Tauchi T, Takaku T, Okabe S, Akahane D, Sashida G, et al. Identification and functional signature of genes regulated by structurally different ABL kinase inhibitors. Oncogene. 2007;26:4179-88 pubmed
    ..These findings demonstrate that the additive/synergistic growth inhibition by imatinib and dasatinib may be mediated in part by CDK2 and CDK8. ..
  42. Chang B, Harte R, Cartwright C. RACK1: a novel substrate for the Src protein-tyrosine kinase. Oncogene. 2002;21:7619-29 pubmed
    ..We think that RACK1 is an important Src substrate that signals downstream of growth factor receptor tyrosine kinases and is involved in the regulation of Src function and cell growth. ..
  43. Hester K, Verhelle D, Escoubet Lozach L, Luna R, Rose D, Glass C. Differential repression of c-myc and cdc2 gene expression by ERF and PE-1/METS. Cell Cycle. 2007;6:1594-604 pubmed
  44. Huang C, Liu C, Chuang N. An enhanced association of RACK1 with Abl in cells transfected with oncogenic ras. Int J Biochem Cell Biol. 2008;40:423-31 pubmed
    ..Future studies are planned to differentiate the mechanism operative for RACK1 associated and RACK1 freed Abl in cells transformed with oncogenic ras. ..
  45. Bedford M, Chan D, Leder P. FBP WW domains and the Abl SH3 domain bind to a specific class of proline-rich ligands. EMBO J. 1997;16:2376-83 pubmed
  46. Wong K, Zou X, Merrell K, Patel A, Marcu K, Chellappan S, et al. v-Abl activates c-myc transcription through the E2F site. Mol Cell Biol. 1995;15:6535-44 pubmed
    ..Identification of v-Abl-dependent changes in E2F-binding proteins provides an important link between v-Abl, transcription, cell cycle regulation, and control of cellular growth...
  47. Rosenbaum H, Harris A, Bath M, McNeall J, Webb E, Adams J, et al. An E mu-v-abl transgene elicits plasmacytomas in concert with an activated myc gene. EMBO J. 1990;9:897-905 pubmed
    ..Moreover, progeny of a cross with analogous E mu-myc mice rapidly developed oligoclonal plasmacytomas. Thus, the collusion of v-abl with c-myc is stage specific, efficiently transforming plasma cells but not pre-B cells or B cells. ..
  48. Hevezi P, Alin K, Rees Jones R, Goff S. Bone marrow-transforming activity of linker insertion mutants of Abelson murine leukemia virus. Oncogene. 1992;7:2323-8 pubmed
    ..We conclude that there is a broad requirement for an intact C-terminal domain of the v-abl protein for the transformation of pre-B cells, but that no single part of this domain is critical. ..
  49. Bolitho P, Street S, Westwood J, Edelmann W, MacGregor D, Waring P, et al. Perforin-mediated suppression of B-cell lymphoma. Proc Natl Acad Sci U S A. 2009;106:2723-8 pubmed publisher
    ..These transgenic models have allowed us to distinguish the role of pfp in surveillance of B-cell lymphomagenesis, as opposed to its loss simply driving the onset of a spontaneous lymphoma characteristic of pfp deficiency. ..
  50. Holcomb M, Rufini A, BarilĂ  D, Klemke R. Deregulation of proteasome function induces Abl-mediated cell death by uncoupling p130CAS and c-CrkII. J Biol Chem. 2006;281:2430-40 pubmed
    ..Our findings indicate that regulated protein degradation by the proteasome specifically controls cell death through regulation of Abl-mediated Crk Tyr221 phosphorylation and assembly of the CAS-Crk signaling scaffold. ..
  51. Jahn T, Seipel P, Coutinho S, Miething C, Peschel C, Duyster J. Grb4/Nckbeta acts as a nuclear repressor of v-Abl-induced transcription from c-jun/c-fos promoter elements. J Biol Chem. 2001;276:43419-27 pubmed
    ..Our results suggest a novel role for Grb4 in the inhibition of promitogenic enhancer elements such as 12-O-tetradecanoylphorbol-13-acetate-responsive element and SRE. ..
  52. Li B. c-Abl in oxidative stress, aging and cancer. Cell Cycle. 2005;4:246-8 pubmed
    ..In contrast, c-Abl takes on an auto-inhibiting conformation and its activation requires post-translational modifications such as phosphorylation and myristoylation. The physiological functions of c-Abl remain elusive. ..
  53. Buschbeck M, Hofbauer S, Di Croce L, Keri G, Ullrich A. Abl-kinase-sensitive levels of ERK5 and its intrinsic basal activity contribute to leukaemia cell survival. EMBO Rep. 2005;6:63-9 pubmed
    ..These results suggest that the ability to regulate the cellular abundance of ERK5 contributes to the oncogenic potential of Abl kinases. ..