Domagoj Vucic

Summary

Affiliation: Genentech Inc
Country: USA

Publications

  1. ncbi Targeting IAP (inhibitor of apoptosis) proteins for therapeutic intervention in tumors
    Domagoj Vucic
    Department of Protein Engineering, Genentech, Inc, South San Francisco, CA 94080, USA
    Curr Cancer Drug Targets 8:110-7. 2008
  2. ncbi Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention and Drug Discovery--ESH's Eighth International Conference. October 14-17, 2010, Cascais, Portugal
    Domagoj Vucic
    Genentech Inc, 1 DNA Way, M S 40, South San Francisco, CA 94080, USA
    IDrugs 13:836-9. 2010
  3. pmc Masking MALT1: the paracaspase's potential for cancer therapy
    Domagoj Vucic
    Department of Protein Engineering, Genentech, Inc, South San Francisco, CA 94080, USA
    J Exp Med 206:2309-12. 2009
  4. ncbi The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy
    M C de Almagro
    Department of Early Discovery Biochemistry, Genentech, Inc, South San Francisco, CA 94080, USA
    Exp Oncol 34:200-11. 2012
  5. doi Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death
    Domagoj Vucic
    Department of Early Discovery Biochemistry, Genentech Inc, South San Francisco, California 94080, USA
    Nat Rev Mol Cell Biol 12:439-52. 2011
  6. doi Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1)
    John W Blankenship
    Department of Protein Engineering, Genentech, Inc, 1 DNA Way, M S 40, South San Francisco, CA 94080, USA
    Biochem J 417:149-60. 2009
  7. pmc c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling
    Jasmin N Dynek
    Department of Protein Engineering, Genentech, Inc, South San Francisco, CA 94080, USA
    EMBO J 29:4198-209. 2010
  8. ncbi Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs
    Kerry Zobel
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    ACS Chem Biol 1:525-33. 2006
  9. pmc Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP
    Domagoj Vucic
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Biochem J 385:11-20. 2005
  10. pmc c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation
    Eugene Varfolomeev
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 283:24295-9. 2008

Collaborators

Detail Information

Publications38

  1. ncbi Targeting IAP (inhibitor of apoptosis) proteins for therapeutic intervention in tumors
    Domagoj Vucic
    Department of Protein Engineering, Genentech, Inc, South San Francisco, CA 94080, USA
    Curr Cancer Drug Targets 8:110-7. 2008
    ..Herein, the role of IAP proteins in cancer and strategies toward targeting IAP proteins for therapeutic intervention will be discussed...
  2. ncbi Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention and Drug Discovery--ESH's Eighth International Conference. October 14-17, 2010, Cascais, Portugal
    Domagoj Vucic
    Genentech Inc, 1 DNA Way, M S 40, South San Francisco, CA 94080, USA
    IDrugs 13:836-9. 2010
    ..Investigational drugs discussed include LCL-161 (Novartis) and navitoclax (Abbott Laboratories/Genentech)...
  3. pmc Masking MALT1: the paracaspase's potential for cancer therapy
    Domagoj Vucic
    Department of Protein Engineering, Genentech, Inc, South San Francisco, CA 94080, USA
    J Exp Med 206:2309-12. 2009
    ..New data shows that targeting MALT1 protease activity may be a promising therapeutic strategy for treating aggressive B cell lymphomas...
  4. ncbi The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy
    M C de Almagro
    Department of Early Discovery Biochemistry, Genentech, Inc, South San Francisco, CA 94080, USA
    Exp Oncol 34:200-11. 2012
    ..This article is part of a Special Issue entitled "Apoptosis: Four Decades Later"...
  5. doi Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death
    Domagoj Vucic
    Department of Early Discovery Biochemistry, Genentech Inc, South San Francisco, California 94080, USA
    Nat Rev Mol Cell Biol 12:439-52. 2011
    ..Therapeutic agents that target apoptotic regulatory proteins, including those that are part of the ubiquitin-proteasome system, might afford clinical benefits...
  6. doi Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1)
    John W Blankenship
    Department of Protein Engineering, Genentech, Inc, 1 DNA Way, M S 40, South San Francisco, CA 94080, USA
    Biochem J 417:149-60. 2009
    ..These results suggest that ubiquitin binding may be an important mechanism for rapid turnover of auto-ubiquitinated c-IAP1 and c-IAP2...
  7. pmc c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling
    Jasmin N Dynek
    Department of Protein Engineering, Genentech, Inc, South San Francisco, CA 94080, USA
    EMBO J 29:4198-209. 2010
    ..Lastly, NF-κB essential modifier efficiently binds K11-linked ubiquitin chains, suggesting that this ubiquitin linkage may have a signalling role in the activation of proliferative cellular pathways...
  8. ncbi Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs
    Kerry Zobel
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    ACS Chem Biol 1:525-33. 2006
    ..The compounds are further demonstrated to activate caspase-3 and -7, to reduce cell viability in assays using MDA-MB-231 breast cancer cells and A2058 melanoma cells, and to enhance doxorubicin-induced apoptosis in MDA-MB-231 cells...
  9. pmc Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP
    Domagoj Vucic
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Biochem J 385:11-20. 2005
    ..These results suggest that ML-IAP might regulate apoptosis by sequestering Smac and preventing it from antagonizing XIAP-mediated inhibition of caspases, rather than by direct inhibition of caspases...
  10. pmc c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation
    Eugene Varfolomeev
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 283:24295-9. 2008
    ..Therefore, c-IAP1 and c-IAP2 are required for TNFalpha-stimulated RIP1 ubiquitination and NF-kappaB activation...
  11. doi Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists
    Chudi Ndubaku
    Departments of Medicinal Chemistry and Protein Engineering, Genentech, Inc, South San Francisco, CA 94080, USA
    ACS Chem Biol 4:557-66. 2009
    ..Therefore, although compounds that specifically target c-IAP1 and c-IAP2 are capable of inducing apoptosis, antagonism of the c-IAP proteins and XIAP is required for efficient induction of cancer cell death by IAP antagonists...
  12. ncbi IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis
    Eugene Varfolomeev
    Department of Protein Engineering, Genentech, Inc, South San Francisco, CA 94080, USA
    Cell 131:669-81. 2007
    ..Through their ubiquitin E3 ligase activities c-IAP1 and c-IAP2 promote proteasomal degradation of NIK, the central ser/thr kinase in the noncanonical NF-kappaB pathway...
  13. pmc Improved quantitative mass spectrometry methods for characterizing complex ubiquitin signals
    Lilian Phu
    Departments of Protein Chemistry, Genentech, Inc, South San Francisco, California 94080, USA
    Mol Cell Proteomics 10:M110.003756. 2011
    ..By combining these two powerful tools, we show that polyubiquitinated substrates purified from cells can be modified by mixtures of K48, K63, and K11 linkages...
  14. ncbi The inhibitor of apoptosis protein fusion c-IAP2.MALT1 stimulates NF-kappaB activation independently of TRAF1 AND TRAF2
    Eugene Varfolomeev
    Departments of Protein Engineering and Physiological Chemistry, Genentech, Inc, South San Francisco, California 94110, USA
    J Biol Chem 281:29022-9. 2006
    ..Therefore, the t(11, 18)(q21;q21) translocation creating the c-IAP2.MALT1 fusion protein activates NF-kappaB and contributes to human malignancy in the absence of signaling adaptors that might otherwise regulate its activity...
  15. doi Characterization of ML-IAP protein stability and physiological role in vivo
    Eugene Varfolomeev
    Department of Early Discovery Biochemistry, Genentech Inc, South San Francisco, CA 94080, USA
    Biochem J 447:427-36. 2012
    ..The results of the present study indicate that ML-IAP is dispensable for both normal mouse development and ocular homoeostasis...
  16. pmc X chromosome-linked inhibitor of apoptosis regulates cell death induction by proapoptotic receptor agonists
    Eugene Varfolomeev
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 284:34553-60. 2009
    ....
  17. doi Cellular inhibitors of apoptosis are global regulators of NF-κB and MAPK activation by members of the TNF family of receptors
    Eugene Varfolomeev
    Department of Early Discovery Biochemistry, Genentech Inc, South San Francisco, CA 94080, USA
    Sci Signal 5:ra22. 2012
    ..These results define c-IAP proteins as critical regulators of the activation of NF-κB and MAPK signaling pathways by members of the TNFR superfamily...
  18. doi Microphthalmia-associated transcription factor is a critical transcriptional regulator of melanoma inhibitor of apoptosis in melanomas
    Jasmin N Dynek
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    Cancer Res 68:3124-32. 2008
    ..Collectively, these findings implicate MITF as a major transcriptional regulator of ML-IAP expression in melanomas, and suggest that ML-IAP contributes to the prosurvival activity of MITF in melanoma progression...
  19. doi Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination
    Erin C Dueber
    Department of Early Discovery Biochemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
    Science 334:376-80. 2011
    ..Antagonist binding induces conformational rearrangements that enable RING dimerization and formation of the active E3 ligase...
  20. pmc OTUB1 modulates c-IAP1 stability to regulate signalling pathways
    Tatiana Goncharov
    Department of Early Discovery Biochemistry, Genentech, Inc, South San Francisco, CA 94080, USA
    EMBO J 32:1103-14. 2013
    ..These results suggest that OTUB1 regulates NF-κB and MAPK signalling pathways and TNF-dependent cell death by modulating c-IAP1 stability...
  21. doi Targeting inhibitor of apoptosis proteins for therapeutic intervention
    Chudi Ndubaku
    Department of Medicinal Chemistry, Genentech, Inc, South San Francisco, CA 94080, USA
    Future Med Chem 1:1509-25. 2009
    ..In addition, several other IAP-targeting strategies, including antisense oligonucleotides and transcriptional repression, have also been initiated, with the hope of providing therapeutic benefit to cancer patients...
  22. pmc Targeting p21-activated kinase 1 (PAK1) to induce apoptosis of tumor cells
    Christy C Ong
    Department of Translational Oncology, Genentech, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 108:7177-82. 2011
    ..Together, our results provide evidence for dysregulation of PAK1 in breast and squamous NSCLCs and a role for PAK1 in cellular survival and proliferation in these indications...
  23. ncbi Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP)
    Matthew C Franklin
    Department of Protein Engineering, Genentech, Inc, One DNA Way, South San Francisco, California 94080, USA
    Biochemistry 42:8223-31. 2003
    ....
  24. doi Antagonists of IAP proteins as cancer therapeutics
    Jasmin N Dynek
    Department of Protein Engineering, Genentech, Inc, South San Francisco, CA 94080, USA
    Cancer Lett 332:206-14. 2013
    ..In this review we will discuss the role of IAP proteins in cancer and the development of antagonists targeting IAP proteins for cancer treatment...
  25. ncbi Molecular determinants of kinase pathway activation by Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand
    Eugene Varfolomeev
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 280:40599-608. 2005
    ..One function of kinase stimulation by Apo2L/TRAIL may be to promote phagocytic engulfment of apoptotic cells...
  26. pmc Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152)
    John A Flygare
    Department of Discovery Chemistry, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    J Med Chem 55:4101-13. 2012
    ..049 to 1.48 mg/kg) tested. Mean plasma clearance in humans was 9 ± 3 mL/min/kg, and the volume of distribution was 0.6 ± 0.2 L/kg...
  27. doi Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold
    Frederick Cohen
    Departments of Discovery Chemistry, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    J Med Chem 52:1723-30. 2009
    ..Finally, compound 14b inhibits tumor growth when dosed orally in a breast cancer xenograft model...
  28. ncbi Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf
    Sanjeev Mariathasan
    Molecular Oncology Department, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 430:213-8. 2004
    ..Notably, cell death triggered by stimuli that engage caspase-1 was ablated in macrophages lacking either ASC or Ipaf, suggesting a coupling between the inflammatory and cell death pathways...
  29. ncbi The inhibitor of apoptosis proteins as therapeutic targets in cancer
    Domagoj Vucic
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    Clin Cancer Res 13:5995-6000. 2007
    ..Here, we discuss the role of IAP proteins in cancer and options for targeting IAP proteins for therapeutic intervention...
  30. doi Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis
    Kim Newton
    Department of Physiological Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
    Science 343:1357-60. 2014
    ..Our data indicate that the kinase activity of RIPK3 is essential for necroptosis but also governs whether a cell activates caspase-8 and dies by apoptosis. ..
  31. doi Protease activity of MALT1: a mystery unravelled
    Daniel Kirchhofer
    Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA 94080, USA
    Biochem J 444:e3-5. 2012
    ....
  32. doi Inhibitor of apoptosis proteins: fascinating biology leads to attractive tumor therapeutic targets
    Eugene Varfolomeev
    Department of Early Discovery Biochemistry, Genentech Inc, 1 DNA Way, M S 40, South San Francisco, CA 94080, USA
    Future Oncol 7:633-48. 2011
    ..Other strategies involve antisense nucleotides and transcriptional repression. The main focus of this article is to provide an update on IAP protein biology and perspectives on the development of IAP-targeting therapeutics...
  33. ncbi (Un)expected roles of c-IAPs in apoptotic and NFkappaB signaling pathways
    Eugene Varfolomeev
    Department of Protein Engineering, Genentech, Inc South San Francisco, California 94080, USA
    Cell Cycle 7:1511-21. 2008
    ..Here, we discuss the most recent progress in our understanding of the biological roles of c-IAPs, as well as the implications of targeting c-IAPs for therapeutic intervention...
  34. pmc POPing the fire into the pyrin?
    Sanjeev Mariathasan
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, CA 94080, USA
    Biochem J 373:e1-2. 2003
    ..identifies a new member of the pyrin family that may control signalling by sequestering pro-inflammatory components, shedding light on the origin of human inflammatory disorders...
  35. ncbi Ubiquitin ligases in cancer: ushers for degradation
    Kim Newton
    Department of Physiological Chemistry, Genentech, Inc, South San Francisco, California 94110, USA
    Cancer Invest 25:502-13. 2007
    ....
  36. ncbi SMAC negatively regulates the anti-apoptotic activity of melanoma inhibitor of apoptosis (ML-IAP)
    Domagoj Vucic
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 277:12275-9. 2002
    ..These results demonstrate the feasibility of using SMAC peptides as a way to sensitize IAP-expressing cells to pro-apoptotic stimuli such as chemotherapeutic agents...
  37. ncbi Apoptotic pathways as targets for therapeutic intervention
    Domagoj Vucic
    Curr Cancer Drug Targets 8:86. 2008