bcl 2 homologous antagonist killer protein


Summary: A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.

Top Publications

  1. Banadyga L, Veugelers K, Campbell S, Barry M. The fowlpox virus BCL-2 homologue, FPV039, interacts with activated Bax and a discrete subset of BH3-only proteins to inhibit apoptosis. J Virol. 2009;83:7085-98 pubmed publisher
    ..Collectively, our data suggest that FPV039 inhibits apoptosis by sequestering and inactivating multiple proapoptotic Bcl-2 proteins, including certain BH3-only proteins and both of the critical "gatekeepers" of apoptosis, Bak and Bax...
  2. Steimer D, Boyd K, Takeuchi O, Fisher J, Zambetti G, Opferman J. Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function. Blood. 2009;113:2805-15 pubmed publisher
    ..Thus, MCL-1 plays selective roles in myeloid development, being required for neutrophil development and setting the threshold for apoptosis during a macrophage effector response. ..
  3. Manara A, Lindsay J, Marchioretto M, Astegno A, Gilmore A, Esposti M, et al. Bid binding to negatively charged phospholipids may not be required for its pro-apoptotic activity in vivo. Biochim Biophys Acta. 2009;1791:997-1010 pubmed publisher
    ..The results are interpreted in relation to an underlying interaction of Bid with lysophosphatidylcholine, which is not disrupted in any mutant retaining pro-apoptotic function both in vitro and in vivo...
  4. Ren D, Kim H, Tu H, Westergard T, Fisher J, Rubens J, et al. The VDAC2-BAK rheostat controls thymocyte survival. Sci Signal. 2009;2:ra48 pubmed publisher
    ..Thus, the VDAC2-BAK axis provides a mechanism that governs the homeostasis of thymocytes. Our study reveals a sophisticated built-in rheostat that likely fine-tunes immune competence to balance autoimmunity and immunodeficiency. ..
  5. Venticinque L, Meruelo D. Sindbis viral vector induced apoptosis requires translational inhibition and signaling through Mcl-1 and Bak. Mol Cancer. 2010;9:37 pubmed publisher
    ..A comprehensive understanding of the mechanism of apoptosis would facilitate the design of more effective vectors for cancer therapy...
  6. Yahiro K, Morinaga N, Moss J, Noda M. Subtilase cytotoxin induces apoptosis in HeLa cells by mitochondrial permeabilization via activation of Bax/Bak, independent of C/EBF-homologue protein (CHOP), Ire1alpha or JNK signaling. Microb Pathog. 2010;49:153-63 pubmed publisher
  7. Liu X, Bera T, Liu L, Pastan I. A primate-specific POTE-actin fusion protein plays a role in apoptosis. Apoptosis. 2009;14:1237-44 pubmed publisher
    ..Our data indicates that the POTE gene family encodes a new family of proapoptotic proteins. ..
  8. Lim D, Park J. Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin. Am J Physiol Gastrointest Liver Physiol. 2009;296:G1060-8 pubmed publisher
    ..The induction of p53 results in the translocation of Bax to the mitochondria, which contributes to fisetin-induced apoptosis in HCT-116 cells. ..
  9. Owens T, Foster F, Valentijn A, Gilmore A, Streuli C. Role for X-linked Inhibitor of apoptosis protein upstream of mitochondrial permeabilization. J Biol Chem. 2010;285:1081-8 pubmed publisher
    ..Moreover, switching the function of proteins from anti- to proapoptotic forms may be a common theme in the efficient execution of cell death. ..

More Information


  1. Ross K, Rudel T, Kozjak Pavlovic V. TOM-independent complex formation of Bax and Bak in mammalian mitochondria during TNFalpha-induced apoptosis. Cell Death Differ. 2009;16:697-707 pubmed publisher
    ..We conclude that the import and assembly machineries of mammalian mitochondria have no impact on the translocation and complex assembly of Bax and Bak upon apoptosis induction. ..
  2. Kim H, Tu H, Ren D, Takeuchi O, Jeffers J, Zambetti G, et al. Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol Cell. 2009;36:487-99 pubmed publisher
    ..Accordingly, deficiency of Bim/Puma impedes ER stress-induced BAX/BAK activation and apoptosis. Our study provides mechanistic insights regarding the spatiotemporal execution of BAX/BAK-governed cell death. ..
  3. May K, Paton J, Paton A. Escherichia coli subtilase cytotoxin induces apoptosis regulated by host Bcl-2 family proteins Bax/Bak. Infect Immun. 2010;78:4691-6 pubmed publisher
  4. Zhang H, Li M, Han Y, Hong L, Gong T, Sun L, et al. Down-regulation of miR-27a might reverse multidrug resistance of esophageal squamous cell carcinoma. Dig Dis Sci. 2010;55:2545-51 pubmed publisher
    ..MiR-27a might play important roles in multidrug resistance of esophageal cancer. The further study of the biological functions of miR-27a might be helpful for developing possible strategies to treat esophageal cancer. ..
  5. Siskind L, Mullen T, Romero Rosales K, Clarke C, Hernandez Corbacho M, Edinger A, et al. The BCL-2 protein BAK is required for long-chain ceramide generation during apoptosis. J Biol Chem. 2010;285:11818-26 pubmed publisher
    ..By establishing a unique role for BAK in long-chain ceramide metabolism, these studies further demonstrate that the seemingly redundant proteins BAK and BAX have distinct mechanisms of action during apoptosis induction. ..
  6. Elayat G, Selim A, Wells C. Cell turnover in apocrine metaplasia and apocrine adenosis of the breast. Ann Diagn Pathol. 2010;14:1-7 pubmed publisher
    ..Further studies are needed to study other apoptotic pathways that may be involved in cell turnover in these lesions. ..
  7. Shi M, Wang H, Xie S, Luo Y, Sun C, Chen X, et al. Antimicrobial peptaibols, novel suppressors of tumor cells, targeted calcium-mediated apoptosis and autophagy in human hepatocellular carcinoma cells. Mol Cancer. 2010;9:26 pubmed publisher
    ..Taken together, these findings showed for the first time that peptaibols were novel regulators involved in both apoptosis and autophagy, suggesting that the class of peptaibols might serve as potential suppressors of tumor cells. ..
  8. Autret A, Martin S. Emerging role for members of the Bcl-2 family in mitochondrial morphogenesis. Mol Cell. 2009;36:355-63 pubmed publisher
    ..Here we review this emerging area and argue for a role for the Bcl-2 family as novel regulators of mitochondrial morphogenesis. ..
  9. Nogueira C, Lindsten T, Jamieson A, Case C, Shin S, Thompson C, et al. Rapid pathogen-induced apoptosis: a mechanism used by dendritic cells to limit intracellular replication of Legionella pneumophila. PLoS Pathog. 2009;5:e1000478 pubmed publisher
    ..pneumophila replication in DCs. Thus, DCs have a microbial response pathway that rapidly activates apoptosis to limit pathogen replication. ..
  10. Madesh M, Zong W, Hawkins B, Ramasamy S, Venkatachalam T, Mukhopadhyay P, et al. Execution of superoxide-induced cell death by the proapoptotic Bcl-2-related proteins Bid and Bak. Mol Cell Biol. 2009;29:3099-112 pubmed publisher
  11. Delgado Vega A, Castiblanco J, Gomez L, Diaz Gallo L, Rojas Villarraga A, Anaya J. Bcl-2 antagonist killer 1 (BAK1) polymorphisms influence the risk of developing autoimmune rheumatic diseases in women. Ann Rheum Dis. 2010;69:462-5 pubmed publisher
    ..The results indicate that the BAK1 polymorphisms influence the risk of acquiring AIRDs in the population studied and are consistent with the paradigm that autoimmune diseases are likely to share common susceptibility variants. ..
  12. Uhl M, Kepp O, Jusforgues Saklani H, Vicencio J, Kroemer G, Albert M. Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8+ T cells. Cell Death Differ. 2009;16:991-1005 pubmed publisher
    ..We predict that targeting the autophagy cascade may provide a therapeutic strategy for achieving robust cross-priming of viral and tumor-specific CD8(+) T cells. ..
  13. Martin A, Mitchell C, Rahmani M, Nephew K, Grant S, Dent P. Inhibition of MCL-1 enhances lapatinib toxicity and overcomes lapatinib resistance via BAK-dependent autophagy. Cancer Biol Ther. 2009;8:2084-96 pubmed
    ..Collectively, our data demonstrate that Obatoclax mediated inhibition of MCL-1 rapidly enhances Lapatinib toxicity in tumor cells via a toxic form of autophagy and via AIF release from the mitochondrion. ..
  14. Guo S, Lu J, Schlanger R, Zhang H, Wang J, Fox M, et al. MicroRNA miR-125a controls hematopoietic stem cell number. Proc Natl Acad Sci U S A. 2010;107:14229-34 pubmed publisher
    ..These data demonstrate cell-state-specific regulation by microRNA and identify a unique microRNA functioning to regulate the stem cell pool size. ..
  15. Kutuk O, Arisan E, Tezil T, Shoshan M, Basaga H. Cisplatin overcomes Bcl-2-mediated resistance to apoptosis via preferential engagement of Bak: critical role of Noxa-mediated lipid peroxidation. Carcinogenesis. 2009;30:1517-27 pubmed publisher
  16. Snyder C, Shroff E, Liu J, Chandel N. Nitric oxide induces cell death by regulating anti-apoptotic BCL-2 family members. PLoS ONE. 2009;4:e7059 pubmed publisher
    ..However, scavengers of ROS or peroxynitrite do not prevent NO-induced cell death. Collectively, these data indicate that NO degrades MCL-1 through the ASK1-JNK1 axis to induce BAX/BAK-dependent cell death. ..
  17. Cerella C, Scherer C, Cristofanon S, Henry E, Anwar A, Busch C, et al. Cell cycle arrest in early mitosis and induction of caspase-dependent apoptosis in U937 cells by diallyltetrasulfide (Al2S4). Apoptosis. 2009;14:641-54 pubmed publisher
  18. Waxman A, Kolliputi N. IL-6 protects against hyperoxia-induced mitochondrial damage via Bcl-2-induced Bak interactions with mitofusins. Am J Respir Cell Mol Biol. 2009;41:385-96 pubmed publisher
    ..Taken together, our results suggest that IL-6 induces Bcl-2 expression to perform cytoprotective functions in response to oxygen toxicity, and that this effect is mediated by alterations in the interactions between Bak and Mfns. ..
  19. Martinez Caballero S, Dejean L, Kinnally M, Oh K, Mannella C, Kinnally K. Assembly of the mitochondrial apoptosis-induced channel, MAC. J Biol Chem. 2009;284:12235-45 pubmed publisher
    ..5-6 nm. The mitochondrial permeability data are inconsistent with formation of lipidic pores capable of transporting megadalton-sized macromolecules as observed with recombinant Bax in liposomes. ..
  20. Haag P, Viktorsson K, Lindberg M, Kanter L, Lewensohn R, Stenke L. Deficient activation of Bak and Bax confers resistance to gemtuzumab ozogamicin-induced apoptotic cell death in AML. Exp Hematol. 2009;37:755-66 pubmed publisher
    ..Our novel data on GO-induced proapoptotic activation of Bax, Bak, and stress-activated protein kinase indicate an important role for these signal proteins in the regulation of GO sensitivity in AML. ..
  21. Samudio I, Harmancey R, Fiegl M, Kantarjian H, Konopleva M, Korchin B, et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest. 2010;120:142-56 pubmed publisher
    ..The results support the concept of FAO inhibitors as a therapeutic strategy in hematological malignancies. ..
  22. Fontanini A, Foti C, Potu H, Crivellato E, Maestro R, Bernardi P, et al. The Isopeptidase Inhibitor G5 Triggers a Caspase-independent Necrotic Death in Cells Resistant to Apoptosis: A COMPARATIVE STUDY WITH THE PROTEASOME INHIBITOR BORTEZOMIB. J Biol Chem. 2009;284:8369-81 pubmed publisher
    ..The importance of cell adhesion impairment in the G5-induced necrotic death of DKO cells was confirmed by the antagonist effect of the extracellular matrix-adhesive components, collagen and fibronectin. ..
  23. Gomez J, Sun W, Gama V, Hajkova D, Yoshida T, Wu Z, et al. The C-terminus of interferon gamma receptor beta chain (IFNgammaR2) has antiapoptotic activity as a Bax inhibitor. Cancer Biol Ther. 2009;8:1771-86 pubmed
    ..Our discovery of the anti-Bax activity of the cytoplasmic domain of IFNgammaR2 may shed new light on the mechanism of how cell death is controlled by IFNgamma and Bax. ..
  24. Produit Zengaffinen N, Pournaras C, Schorderet D. Retinal ischemia-induced apoptosis is associated with alteration in Bax and Bcl-x(L) expression rather than modifications in Bak and Bcl-2. Mol Vis. 2009;15:2101-10 pubmed
    ..We showed that the Bax:Bcl-2 and Bax:Bcl-x(L) balances were not affected in the initial phases, but the Bax:Bcl-x(L) ratio shifted toward apoptosis during the late phase of recovery. This shift was reinforced by caspase-3 upregulation. ..
  25. Jiang C, Wroblewski D, Yang F, Hersey P, Zhang X. Human melanoma cells under endoplasmic reticulum stress are more susceptible to apoptosis induced by the BH3 mimetic obatoclax. Neoplasia. 2009;11:945-55 pubmed
  26. Liguori L, Lenormand J. Production of recombinant proteoliposomes for therapeutic uses. Methods Enzymol. 2009;465:209-23 pubmed publisher
    ..Furthermore, this system can be easily adapted for producing "difficult to express proteins" compared with the classical overexpression (bacterial or eukaryotic) systems. ..
  27. Dussmann H, Rehm M, Concannon C, Anguissola S, Würstle M, Kacmar S, et al. Single-cell quantification of Bax activation and mathematical modelling suggest pore formation on minimal mitochondrial Bax accumulation. Cell Death Differ. 2010;17:278-90 pubmed publisher
  28. Reiners J, Agostinis P, Berg K, Oleinick N, Kessel D. Assessing autophagy in the context of photodynamic therapy. Autophagy. 2010;6:7-18 pubmed
    ..Finally, an aborted autophagic response occurs in cells with photodamaged lysosomes. Whereas autophagosomes form, digestion of their cargo is compromised because of the absence of functional lysosomes. ..
  29. Dharmapuri S, Aurisicchio L, Biondo A, Welsh N, Ciliberto G, La Monica N. Antiapoptotic small interfering RNA as potent adjuvant of DNA vaccination in a mouse mammary tumor model. Hum Gene Ther. 2009;20:589-97 pubmed publisher
    ..These data demonstrate that some siRNA sequences can act in concert with DNA-EP to control HER2/neu-positive mammary carcinoma. These observations emphasize the potential of siRNA as adjuvant for therapeutic DNA vaccines. ..
  30. Ghiotto F, Fais F, Tenca C, Tomati V, Morabito F, Casciaro S, et al. Apoptosis of B-cell chronic lymphocytic leukemia cells induced by a novel BH3 peptidomimetic. Cancer Biol Ther. 2009;8:263-71 pubmed
    ..Altogether, we demonstrate that 072RB induces significant apoptosis of B-CLL cells subsequent to Bcl-X(L) and Mcl-1 downregulation. ..
  31. Hassan M, Feyen O, Grinstein E. Fas-induced apoptosis of renal cell carcinoma is mediated by apoptosis signal-regulating kinase 1 via mitochondrial damage-dependent caspase-8 activation. Cell Oncol. 2009;31:437-56 pubmed publisher
    ..Thus, the described molecular mechanisms of CH11-induced apoptosis suggest the reliability of Fas activation as an alternative therapeutic approach for the treatment of patients with advanced renal cell carcinoma. ..
  32. Rambal A, Panaguiton Z, Kramer L, Grant S, Harada H. MEK inhibitors potentiate dexamethasone lethality in acute lymphoblastic leukemia cells through the pro-apoptotic molecule BIM. Leukemia. 2009;23:1744-54 pubmed publisher
    ..This study provides a rational foundation for future attempts to improve the activity of GCs with clinically relevant pharmacologic MEK inhibitors in the treatment of ALL and possibly other hematologic malignancies. ..
  33. Du X, Youle R, FitzGerald D, Pastan I. Pseudomonas exotoxin A-mediated apoptosis is Bak dependent and preceded by the degradation of Mcl-1. Mol Cell Biol. 2010;30:3444-52 pubmed publisher
    ..Overexpression of Mcl-1 and Bcl-x(L) inhibited PE-induced MEF death. Our data suggest that Bak is the preferential mediator of PE-mediated apoptosis and that the rapid degradation of Mcl-1 unleashes Bak to activate apoptosis. ..
  34. Jiang M, Wang C, Huang S, Yang T, Dong Z. Cisplatin-induced apoptosis in p53-deficient renal cells via the intrinsic mitochondrial pathway. Am J Physiol Renal Physiol. 2009;296:F983-93 pubmed publisher
    ..Together, the results have demonstrated a p53-independent mechanism of cisplatin nephrotoxicity that involves the mitochondrial pathway of apoptosis. ..
  35. Schoenwaelder S, Yuan Y, Josefsson E, White M, Yao Y, Mason K, et al. Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function. Blood. 2009;114:663-6 pubmed publisher
    ..These studies show the existence of 2 distinct pathways regulating the procoagulant function of platelets. ..
  36. Someya S, Prolla T. Mitochondrial oxidative damage and apoptosis in age-related hearing loss. Mech Ageing Dev. 2010;131:480-6 pubmed publisher
    ..We also propose that this mechanism may be of general relevance to age-related cell death in long-lived post-mitotic cells of multiple tissues, providing an opportunity for a targeted therapeutic intervention in human aging. ..
  37. Karlberg M, Ekoff M, Huang D, Mustonen P, Harvima I, Nilsson G. The BH3-mimetic ABT-737 induces mast cell apoptosis in vitro and in vivo: potential for therapeutics. J Immunol. 2010;185:2555-62 pubmed publisher
  38. Oh K, Singh P, Lee K, Foss K, Lee S, Park M, et al. Conformational changes in BAK, a pore-forming proapoptotic Bcl-2 family member, upon membrane insertion and direct evidence for the existence of BH3-BH3 contact interface in BAK homo-oligomers. J Biol Chem. 2010;285:28924-37 pubmed publisher
    ..Detailed analyses of the data provide new insights into the structure of the BAX or BAK homodimer. ..
  39. Yamaguchi R, Lartigue L, Perkins G, Scott R, Dixit A, Kushnareva Y, et al. Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization. Mol Cell. 2008;31:557-69 pubmed publisher
    ..Thus, apoptosis requires a subtle form of Opa1-dependent crista remodeling that is induced by BH3-only proteins and Bax/Bak but independent of MOMP. ..
  40. Depalo R, Cavallini A, Lorusso F, Bassi E, Totaro I, Marzullo A, et al. Apoptosis in normal ovaries of women with and without endometriosis. Reprod Biomed Online. 2009;19:808-15 pubmed
    ..In conclusion, the reduction of apoptosis in unaffected tissue in women with endometriosis suggests that they may be predisposed to develop endometriosis. ..
  41. Dewson G, Kratina T, Czabotar P, Day C, Adams J, Kluck R. Bak activation for apoptosis involves oligomerization of dimers via their alpha6 helices. Mol Cell. 2009;36:696-703 pubmed publisher
    ..We conclude that alpha6:alpha6 interaction occurs during Bak oligomerization and proapoptotic function, but we find no evidence that zinc binding to that interface regulates apoptosis. ..
  42. Morin D, Assaly R, Paradis S, Berdeaux A. Inhibition of mitochondrial membrane permeability as a putative pharmacological target for cardioprotection. Curr Med Chem. 2009;16:4382-98 pubmed
    ..The objective of this review is to examine the pharmacological strategies capable of inhibiting mitochondrial membrane permeabilization induced by myocardial ischemia-reperfusion. ..
  43. Tang C, Chiu Y, Huang C, Chen Y, Chen P. Arsenic induces cell apoptosis in cultured osteoblasts through endoplasmic reticulum stress. Toxicol Appl Pharmacol. 2009;241:173-81 pubmed publisher
    ..Transfection of cells with GRP78 or calpain siRNA reduced As-mediated cell apoptosis in osteoblasts. Therefore, our results suggest that As increased cell apoptosis in cultured osteoblasts and increased the risk of osteoporosis. ..
  44. Klee M, Pallauf K, Alcala S, Fleischer A, Pimentel Muiños F. Mitochondrial apoptosis induced by BH3-only molecules in the exclusive presence of endoplasmic reticular Bak. EMBO J. 2009;28:1757-68 pubmed publisher
  45. Yao Y, Marassi F. BAX and BAK caught in the act. Mol Cell. 2009;36:353-4 pubmed publisher
    ..2009) describe the steps involved in the direct activation of the proapoptotic proteins BAX and BAK by their BH3-only partners, resolving the controversy regarding direct versus indirect activation of these proteins. ..
  46. Someya S, Xu J, Kondo K, Ding D, Salvi R, Yamasoba T, et al. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. Proc Natl Acad Sci U S A. 2009;106:19432-7 pubmed publisher
    ..Thus, induction of a Bak-dependent mitochondrial apoptosis program in response to oxidative stress is a key mechanism of AHL in C57BL/6J mice. ..
  47. Del Vecchio A, Silva J, Silva J, Andreotti P, Soares C, Benard G, et al. Induction of apoptosis in A549 pulmonary cells by two Paracoccidioides brasiliensis samples. Mem Inst Oswaldo Cruz. 2009;104:749-54 pubmed
    ..The overall mechanism is a complex process, which may involve several signal transduction pathways. These findings could partially explain the efficient behaviour of this fungus in promoting tissue infection and/or blood dissemination. ..
  48. Kaddour Djebbar I, Choudhary V, Brooks C, Ghazaly T, Lakshmikanthan V, Dong Z, et al. Specific mitochondrial calcium overload induces mitochondrial fission in prostate cancer cells. Int J Oncol. 2010;36:1437-44 pubmed
    ..Thus, our results show that combination of an apoptogenic agent and an appropriate calcium channel blocker provide therapeutic advantages. ..
  49. Klamt F, Zdanov S, Levine R, Pariser A, Zhang Y, Zhang B, et al. Oxidant-induced apoptosis is mediated by oxidation of the actin-regulatory protein cofilin. Nat Cell Biol. 2009;11:1241-6 pubmed publisher
    ..Exposure of cofilin to TnCl results in intramolecular disulphide bonding and oxidation of Met residues to Met sulphoxide, but only Cys oxidation causes cofilin to induce mitochondrial damage. ..
  50. Rudner J, Elsaesser S, Müller A, Belka C, Jendrossek V. Differential effects of anti-apoptotic Bcl-2 family members Mcl-1, Bcl-2, and Bcl-xL on celecoxib-induced apoptosis. Biochem Pharmacol. 2010;79:10-20 pubmed publisher
  51. Vogler M, Weber K, Dinsdale D, Schmitz I, Schulze Osthoff K, Dyer M, et al. Different forms of cell death induced by putative BCL2 inhibitors. Cell Death Differ. 2009;16:1030-9 pubmed publisher
  52. Festuccia C, Gravina G, D Alessandro A, Muzi P, Millimaggi D, Dolo V, et al. Azacitidine improves antitumor effects of docetaxel and cisplatin in aggressive prostate cancer models. Endocr Relat Cancer. 2009;16:401-13 pubmed publisher
    ..Our results provide a rationale for clinical trials on combination treatments with azacitidine in patients with hormone-refractory and chemoresistant prostate tumors. ..
  53. Takahashi Y, Karbowski M, Yamaguchi H, Kazi A, Wu J, Sebti S, et al. Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis. Mol Cell Biol. 2005;25:9369-82 pubmed
    ..Taken together, these findings support the notion that Bif-1 is an important component of the mitochondrial pathway for apoptosis as a novel Bax/Bak activator, and loss of this proapoptotic molecule may contribute to tumorigenesis. ..