Experts and Doctors on apoptosis regulatory proteins in Boston, Massachusetts, United States


Locale: Boston, Massachusetts, United States
Topic: apoptosis regulatory proteins

Top Publications

  1. Sandra F, Degli Esposti M, Ndebele K, Gona P, Knight D, Rosenquist M, et al. Tumor necrosis factor-related apoptosis-inducing ligand alters mitochondrial membrane lipids. Cancer Res. 2005;65:8286-97 pubmed
    ..We also show that preservation of phosphatidylcholine homeostasis by inhibition of lipid-degrading enzymes almost completely impedes the activation of pro-caspase-9 while scarcely changing the activation of caspase-8. ..
  2. Zhang X, Jin T, Yang H, DeWolf W, Khosravi Far R, Olumi A. Persistent c-FLIP(L) expression is necessary and sufficient to maintain resistance to tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in prostate cancer. Cancer Res. 2004;64:7086-91 pubmed
    ..Therefore, persistent expression of c-FLIP(L) is necessary and sufficient to regulate sensitivity to TRAIL-mediated apoptosis in prostate cancer cells. ..
  3. Thompson R, Vardinogiannis I, Gilmore T. The sensitivity of diffuse large B-cell lymphoma cell lines to histone deacetylase inhibitor-induced apoptosis is modulated by BCL-2 family protein activity. PLoS ONE. 2013;8:e62822 pubmed publisher
  4. Song K, Benhaga N, Anderson R, Khosravi Far R. Transduction of tumor necrosis factor-related apoptosis-inducing ligand into hematopoietic cells leads to inhibition of syngeneic tumor growth in vivo. Cancer Res. 2006;66:6304-11 pubmed
    ..This approach may be used further to identify important molecules that regulate the sensitivity of tumor cells to TRAIL-induced cell death in vivo. ..
  5. Aminova L, Siddiq A, Ratan R. Antioxidants, HIF prolyl hydroxylase inhibitors or short interfering RNAs to BNIP3 or PUMA, can prevent prodeath effects of the transcriptional activator, HIF-1alpha, in a mouse hippocampal neuronal line. Antioxid Redox Signal. 2008;10:1989-98 pubmed publisher
    ..The findings offer strategies for minimizing the prodeath effects of HIF-1 in neurologic conditions associated with hypoxia and oxidative stress, such as stroke and spinal cord injury. ..
  6. Rocco J, Leong C, Kuperwasser N, DeYoung M, Ellisen L. p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis. Cancer Cell. 2006;9:45-56 pubmed
    ..Together, these data define a pathway whereby deltaNp63alpha promotes survival in squamous epithelial malignancy by repressing a p73-dependent proapoptotic transcriptional program. ..
  7. Kanai R, Zaupa C, Sgubin D, Antoszczyk S, Martuza R, Wakimoto H, et al. Effect of ?34.5 deletions on oncolytic herpes simplex virus activity in brain tumors. J Virol. 2012;86:4420-31 pubmed publisher
    ..Thus, ?68H-6 represents a new oHSV vector that is safe and effective against a variety of brain tumor models. ..
  8. Faber A, Corcoran R, Ebi H, Sequist L, Waltman B, Chung E, et al. BIM expression in treatment-naive cancers predicts responsiveness to kinase inhibitors. Cancer Discov. 2011;1:352-65 pubmed publisher
    ..These findings suggest assessment of BIM levels in treatment-naïve tumor biopsies may indicate the degree of benefit from single-agent kinase inhibitors in multiple oncogene-addiction paradigms. ..
  9. Park S, Nguyen M, Fischer A, Luke M, Affar E, Dieffenbach P, et al. Par-4 links dopamine signaling and depression. Cell. 2005;122:275-87 pubmed
    ..Remarkably, Par-4DeltaLZ mice display significantly increased depression-like behaviors. Collectively, these results provide evidence that Par-4 constitutes a molecular link between impaired dopamine signaling and depression. ..

More Information


  1. Yang W, Klaman L, Chen B, Araki T, Harada H, Thomas S, et al. An Shp2/SFK/Ras/Erk signaling pathway controls trophoblast stem cell survival. Dev Cell. 2006;10:317-27 pubmed
    ..Bim depletion substantially blocks apoptosis and significantly restores Shp2 null TS cell proliferation, thereby establishing a key mechanism by which FGF4 controls stem cell survival. ..
  2. Russo A, Thiagalingam A, Pan H, Califano J, Cheng K, Ponte J, et al. Differential DNA hypermethylation of critical genes mediates the stage-specific tobacco smoke-induced neoplastic progression of lung cancer. Clin Cancer Res. 2005;11:2466-70 pubmed
    ..We also provide preliminary evidence that peripheral lymphocytes could potentially be used as a surrogate for bronchial epithelial cells to detect altered DNA methylation in smokers. ..
  3. Staton T, Lazarevic V, Jones D, Lanser A, Takagi T, Ishii S, et al. Dampening of death pathways by schnurri-2 is essential for T-cell development. Nature. 2011;472:105-9 pubmed publisher
    ..Our findings uncover a critical regulator of T-cell development that controls the balance between death and differentiation. ..
  4. Adams K, Cooper G. Rapid turnover of mcl-1 couples translation to cell survival and apoptosis. J Biol Chem. 2007;282:6192-200 pubmed
    ..Because of its rapid turnover, Mcl-1 may serve as a convergence point for signals that affect global translation, coupling translation to cell survival and the apoptotic machinery. ..
  5. Kang H, Davis Dusenbery B, Nguyen P, Lal A, Lieberman J, Van Aelst L, et al. Bone morphogenetic protein 4 promotes vascular smooth muscle contractility by activating microRNA-21 (miR-21), which down-regulates expression of family of dedicator of cytokinesis (DOCK) proteins. J Biol Chem. 2012;287:3976-86 pubmed publisher
    ..Thus, this study uncovers a regulatory mechanism of the vSMC phenotype by the BMP4-miR-21 axis through DOCK family proteins. ..
  6. Johnstone R, See R, Sells S, Wang J, Muthukkumar S, Englert C, et al. A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1. Mol Cell Biol. 1996;16:6945-56 pubmed
    ..Significantly, par-4, but not a mutant unable to interact with WT1, rescued growth suppression caused by WT1. Thus, we identified a novel repressor that modulates transcription as well as growth suppression functions of WT1. ..
  7. Yi C, Vakifahmetoglu Norberg H, Yuan J. Integration of apoptosis and metabolism. Cold Spring Harb Symp Quant Biol. 2011;76:375-87 pubmed publisher
    ..The revelation that protein N-?-acetylation is regulated by Bcl-xL, a major antiapoptotic mitochondrial protein, demonstrates a mechanism by which metabolism can regulate the activation of multiple key apoptotic factors simultaneously. ..
  8. Pena Cruz V, McDonough S, Diaz Griffero F, Crum C, Carrasco R, Freeman G. PD-1 on immature and PD-1 ligands on migratory human Langerhans cells regulate antigen-presenting cell activity. J Invest Dermatol. 2010;130:2222-30 pubmed publisher
    ..Thus the PD-1 pathway is active in iLCs and inhibits iLC activities, but expression of receptor and ligands reverses upon maturation and PD-L1 and PD-L2 on mLC function to inhibit T-cell responses. ..
  9. Shen L, Guo J, Santos Berrios C, Wu M. Distinct domains for anti- and pro-apoptotic activities of IEX-1. J Biol Chem. 2006;281:15304-11 pubmed
    ..These findings suggest a critical role of IEX-1 in regulation of intracellular ROS homeostasis, providing new insight into the mechanism underlying IEX-1-mediated cell survival. ..
  10. Dieffenbach P, Haeger C, Coronata A, Choi K, Varelas X, Tschumperlin D, et al. Arterial stiffness induces remodeling phenotypes in pulmonary artery smooth muscle cells via YAP/TAZ-mediated repression of cyclooxygenase-2. Am J Physiol Lung Cell Mol Physiol. 2017;313:L628-L647 pubmed publisher
    ..The ability to interrupt this critical mechanobiological feedback loop and enhance local prostaglandin activity via manipulation of YAP/TAZ signaling presents a highly attractive novel strategy for the treatment of PH. ..
  11. Wu W, Heinrichs S, Xu D, Garrison S, Zambetti G, Adams J, et al. Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by repressing puma. Cell. 2005;123:641-53 pubmed
    ..Thus, Slug functions downstream of p53 in developing blood cells as a critical switch that prevents their apoptosis by antagonizing the trans-activation of puma by p53. ..
  12. Gullà A, Di Martino M, Gallo Cantafio M, Morelli E, Amodio N, Botta C, et al. A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells. Clin Cancer Res. 2016;22:1222-33 pubmed publisher
  13. Barnich N, Hisamatsu T, Aguirre J, Xavier R, Reinecker H, Podolsky D. GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells. J Biol Chem. 2005;280:19021-6 pubmed
    ..GRIM-19 may be a key component in NOD2-mediated innate mucosal responses and serve to regulate intestinal epithelial cell responses to microbes. ..
  14. Hasegawa M, Nelson H, Peters E, Ringstrom E, Posner M, Kelsey K. Patterns of gene promoter methylation in squamous cell cancer of the head and neck. Oncogene. 2002;21:4231-6 pubmed
    ..Tobacco smoking may play an important role in both the occurrence of promoter methylation as well as delineating the precise pathway that eventually results in a tumorigenic phenotype. ..
  15. Kim H, Falet H, Hoffmeister K, Hartwig J. Wiskott-Aldrich syndrome protein (WASp) controls the delivery of platelet transforming growth factor-?1. J Biol Chem. 2013;288:34352-63 pubmed publisher
    ..We conclude that WASp function restricts TGF-?1 secretion in a Cdc42- and Src family kinase-dependent manner and independently of actin assembly. ..
  16. Cao C, Ren X, Kharbanda S, Koleske A, Koleske A, Prasad K, et al. The ARG tyrosine kinase interacts with Siva-1 in the apoptotic response to oxidative stress. J Biol Chem. 2001;276:11465-8 pubmed
    ..These findings support a model in which the activation of ARG by oxidative stress induces apoptosis by a Siva-1-dependent mechanism. ..
  17. Quigley M, Pereyra F, Nilsson B, Porichis F, Fonseca C, Eichbaum Q, et al. Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF. Nat Med. 2010;16:1147-51 pubmed publisher
    ..Thus, inhibitory receptors can cause T cell exhaustion by upregulating genes--such as BATF--that inhibit T cell function. Such genes may provide new therapeutic opportunities to improve T cell immunity to HIV. ..
  18. Berger S, Romero X, Ma C, Wang G, Faubion W, Liao G, et al. SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages. Nat Immunol. 2010;11:920-7 pubmed publisher
    ..Thus, SLAM connects the gram-negative bacterial phagosome to ubiquitous cellular machinery responsible for the control of bacterial killing...
  19. Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, et al. Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J Biol Chem. 2006;281:14474-85 pubmed
    ..100, 15077-15082), we propose that the age-dependent decrease of beclin 1 expression may lead to a reduction of autophagic activity during aging, which in turn promotes the accumulation of mutant Htt and the progression of the disease. ..
  20. Gu J, Dong R, Zhang C, McLaughlin D, Wu M, Schlossman S. Functional interaction of DFF35 and DFF45 with caspase-activated DNA fragmentation nuclease DFF40. J Biol Chem. 1999;274:20759-62 pubmed
  21. Blackburn S, Crawford A, Shin H, Polley A, Freeman G, Wherry E. Tissue-specific differences in PD-1 and PD-L1 expression during chronic viral infection: implications for CD8 T-cell exhaustion. J Virol. 2010;84:2078-89 pubmed publisher
    ..These observations have implications for human chronic infections and for therapeutic interventions based on blockade of the PD-1 pathway. ..
  22. Kim S, Na H, Ding Y, Wang Z, Lee S, Choi M. Autophagy promotes intracellular degradation of type I collagen induced by transforming growth factor (TGF)-?1. J Biol Chem. 2012;287:11677-88 pubmed publisher
    ..Our findings suggest a novel role of autophagy as a cytoprotective mechanism to negatively regulate and prevent excess collagen accumulation in the kidney. ..
  23. Molyneaux B, Arlotta P, Hirata T, Hibi M, Macklis J. Fezl is required for the birth and specification of corticospinal motor neurons. Neuron. 2005;47:817-31 pubmed
  24. Banerjee P, Basu A, Wegiel B, Otterbein L, Mizumura K, Gasser M, et al. Heme oxygenase-1 promotes survival of renal cancer cells through modulation of apoptosis- and autophagy-regulating molecules. J Biol Chem. 2012;287:32113-23 pubmed publisher
    ..Thus, application of chemotherapeutic drugs along with HO-1 inhibitor may elevate therapeutic efficiency by reducing the cytoprotective effects of HO-1 and by simultaneous induction of both apoptosis and autophagy. ..
  25. Lee S, Lee S, Coronata A, Fredenburgh L, Chung S, Perrella M, et al. Carbon monoxide confers protection in sepsis by enhancing beclin 1-dependent autophagy and phagocytosis. Antioxid Redox Signal. 2014;20:432-42 pubmed publisher
    ..Carbon monoxide (CO), when administered at low physiologic doses, can modulate cell proliferation, apoptosis, and inflammation in pre-clinical tissue injury models, though its mechanism of action in sepsis remains unclear...
  26. Liu Y, Quang P, Braggio E, Ngo H, Badalian Very G, Flores L, et al. Novel tumor suppressor function of glucocorticoid-induced TNF receptor GITR in multiple myeloma. PLoS ONE. 2013;8:e66982 pubmed publisher
    ..These findings provide novel insights into the pivotal role of GITR in MM pathogenesis and disease progression. ..
  27. Terragni J, Nayak G, Banerjee S, Medrano J, Graham J, Brennan J, et al. The E-box binding factors Max/Mnt, MITF, and USF1 act coordinately with FoxO to regulate expression of proapoptotic and cell cycle control genes by phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 signaling. J Biol Chem. 2011;286:36215-27 pubmed publisher
    ..These results define a novel E-box-regulated network that functions coordinately with FoxO to regulate transcription of apoptotic and cell cycle regulatory genes downstream of PI 3-kinase/Akt/GSK3 signaling. ..
  28. Shen L, Kim S, Chen C. Sensitization of human pancreatic cancer cells harboring mutated K-ras to apoptosis. PLoS ONE. 2012;7:e40435 pubmed publisher
    ..However, the suppression or loss of PKC disrupts the balance and initiates an apoptotic crisis, in which ROS and p73 appear the potential, key targets. ..
  29. Davis B, Hilyard A, Lagna G, Hata A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature. 2008;454:56-61 pubmed publisher
  30. Polytarchou C, Iliopoulos D, Hatziapostolou M, Kottakis F, Maroulakou I, Struhl K, et al. Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation. Cancer Res. 2011;71:4720-31 pubmed publisher
    ..Taken together, this study identifies a novel Akt2-dependent pathway that is activated by hypoxia and promotes tumor resistance via induction of miR-21. ..
  31. Freeman G, Long A, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027-34 pubmed
    ..PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation. ..
  32. Keir M, Butte M, Freeman G, Sharpe A. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704 pubmed publisher
    ..In this review, we discuss current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential. ..
  33. Segev D, Hoshiya Y, Stephen A, Hoshiya M, Tran T, MacLaughlin D, et al. Mullerian inhibiting substance regulates NFkappaB signaling and growth of mammary epithelial cells in vivo. J Biol Chem. 2001;276:26799-806 pubmed
    ..Furthermore, exposure to MIS in vivo increased apoptosis in the mouse mammary ductal epithelium. Thus, MIS may function as an endogenous hormonal regulator of NFkappaB signaling and growth in the breast. ..
  34. Gordon P, Fisher D. Role for the proapoptotic factor BIM in mediating imatinib-induced apoptosis in a c-KIT-dependent gastrointestinal stromal tumor cell line. J Biol Chem. 2010;285:14109-14 pubmed publisher
  35. Segev D, Ha T, Tran T, Kenneally M, Harkin P, Jung M, et al. Mullerian inhibiting substance inhibits breast cancer cell growth through an NFkappa B-mediated pathway. J Biol Chem. 2000;275:28371-9 pubmed
  36. Patel A, Lin L, Geyer A, Haspel J, An C, Cao J, et al. Autophagy in idiopathic pulmonary fibrosis. PLoS ONE. 2012;7:e41394 pubmed publisher
    ..Autophagy is not induced in pulmonary fibrosis despite activation of pathways known to promote autophagy. Impairment of autophagy by TGF-?(1) may represent a mechanism for the promotion of fibrogenesis in IPF. ..
  37. Ma C, Wang N, Detre C, Wang G, O Keeffe M, Terhorst C. Receptor signaling lymphocyte-activation molecule family 1 (Slamf1) regulates membrane fusion and NADPH oxidase 2 (NOX2) activity by recruiting a Beclin-1/Vps34/ultraviolet radiation resistance-associated gene (UVRAG) complex. J Biol Chem. 2012;287:18359-65 pubmed publisher
  38. Gavathiotis E, Suzuki M, Davis M, Pitter K, Bird G, Katz S, et al. BAX activation is initiated at a novel interaction site. Nature. 2008;455:1076-81 pubmed publisher
    ..Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis. ..
  39. Ramsey M, He L, Forster N, Ory B, Ellisen L. Physical association of HDAC1 and HDAC2 with p63 mediates transcriptional repression and tumor maintenance in squamous cell carcinoma. Cancer Res. 2011;71:4373-9 pubmed publisher
    ..In addition, our findings offer a rationale to apply HDAC inhibitors for SCC treatment. ..
  40. Del Gaizo Moore V, Brown J, Certo M, Love T, Novina C, Letai A. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007;117:112-21 pubmed
    ..Indeed, activator BH3-only occupation of BCL2 may prime cancer cells for death, offering a potential explanation for the marked chemosensitivity of certain cancers that express abundant BCL2, such as CLL and follicular lymphoma. ..
  41. LaBelle J, Katz S, Bird G, Gavathiotis E, Stewart M, Lawrence C, et al. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers. J Clin Invest. 2012;122:2018-31 pubmed publisher
    ..Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death. ..
  42. Anjum R, Roux P, Ballif B, Gygi S, Blenis J. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Curr Biol. 2005;15:1762-7 pubmed
    ..Our results suggest that RSK-mediated phosphorylation of DAPK is a unique mechanism for suppressing the proapoptotic function of this death kinase in healthy cells as well as Ras/Raf-transformed cells. ..
  43. Gotsman I, Grabie N, Dacosta R, Sukhova G, Sharpe A, Lichtman A. Proatherogenic immune responses are regulated by the PD-1/PD-L pathway in mice. J Clin Invest. 2007;117:2974-82 pubmed
    ..Our findings indicate that the PD-1/PD-L pathway has an important role in downregulating proatherogenic T cell response and atherosclerosis by limiting APC-dependent T cell activation. ..
  44. Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong S, et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell. 2006;9:351-65 pubmed
    ..Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival. ..
  45. Becker E, Bonni A. Pin1 mediates neural-specific activation of the mitochondrial apoptotic machinery. Neuron. 2006;49:655-62 pubmed
    ..These findings define a neural-specific mechanism of cell death whereby Pin1 couples phosphorylation of BH3-only proteins to activation of the mitochondrial apoptotic machinery. ..
  46. Baksh S, Tommasi S, Fenton S, Yu V, Martins L, Pfeifer G, et al. The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death. Mol Cell. 2005;18:637-50 pubmed
    ..Our findings identify RASSF1A and MAP-1 as important components between death receptors and the apoptotic machinery and reveal a potential link between tumor suppression and death receptor signaling. ..
  47. Deng J, Shimamura T, Perera S, Carlson N, Cai D, Shapiro G, et al. Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from epidermal growth factor receptor inhibition to the mitochondrion. Cancer Res. 2007;67:11867-75 pubmed
    ..This finding has clear implications for overcoming resistance to erlotinib. Resistance to EGFR inhibition can be modulated by alterations in the intrinsic apoptotic pathway controlled by the BCL-2 family of proteins. ..
  48. Berndt S, Camp N, Skibola C, Vijai J, Wang Z, Gu J, et al. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. Nat Commun. 2016;7:10933 pubmed publisher
    ..2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility. ..
  49. Jean J, Oakes S, Joyce Brady M. The Bax inhibitor-1 gene is differentially regulated in adult testis and developing lung by two alternative TATA-less promoters. Genomics. 1999;57:201-8 pubmed
    ..Since Bax inhibitor-1 functions as a suppressor of apoptosis, its expression could provide a survival advantage for select cell populations during the peak period of apoptosis that occurs at birth. ..