Are you Matthew Pando?

Claim your profile

Publications (3)52.57 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chemotherapeutic agents simultaneously induce transcription factors p53 and NFkappaB. p53 induction can activate an apoptotic program, and resistance to chemotherapy correlates with the loss of a functional p53 pathway. By contrast, NFkappaB prevents apoptosis in response to chemotherapeutic agents. We have analyzed the p53 response in IKK1/2(-/-) MEFs, which lack detectable NFkappaB activity. Compared to WT fibroblasts, IKK1/2(-/-) fibroblasts showed increased cell death and p53 induction in response to the chemotherapeutic agent, doxorubicin. Reconstitution of IKK2, but not IKK1, increased Mdm2 levels and decreased doxorubicin-induced p53 stabilization and cell death. IKK2-mediated effects required its kinase function and were abrogated by coexpression of the dominant negative IkappaBalphaM, implying a role for NFkappaB in blocking chemotherapy-induced p53 and cell death.
    Cancer Cell 07/2002; 1(5):493-503. · 24.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Summary Chemotherapeutic agents simultaneously induce transcription factors p53 and NFB. p53 induction can activate an apo- ptotic program, and resistance to chemotherapy correlates with the loss of a functional p53 pathway. By contrast, NFB prevents apoptosis in response to chemotherapeutic agents. We have analyzed the p53 response in IKK1/2 / MEFs, which lack detectable NFB activity. Compared to WT fibroblasts, IKK1/2 / fibroblasts showed increased cell death and p53 induction in response to the chemotherapeutic agent, doxorubicin. Reconstitution of IKK2, but not IKK1, increased Mdm2 levels and decreased doxorubicin-induced p53 stabilization and cell death. IKK2-mediated effects required its kinase function and were abrogated by coexpression of the dominant negative IBM, implying a role for NFB in blocking chemotherapy-induced p53 and cell death.
    Cancer Cell 06/2002; 1(5):493-503. · 24.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fanconi anemia (FA), a genetic disorder predisposing to aplastic anemia and cancer, is characterized by hypersensitivity to DNA-damaging agents and oxidative stress. Five of the cloned FA proteins (FANCA, FANCC, FANCE, FANCF, FANCG) appear to be involved in a common functional pathway that is required for the monoubiquitination of a sixth gene product, FANCD2. Here, we report that FANCA associates with the IkappaB kinase (IKK) signalsome via interaction with IKK2. Components of the FANCA complex undergo rapid, stimulus-dependent changes in phosphorylation, which are blocked by kinase-inactive IKK2 (IKK2 K > M). When exposed to mitomycin C, cells expressing IKK2 K > M develop a cell cycle abnormality characteristic of FA. Thus, FANCA may function to recruit IKK2, thus providing the cell a means of rapidly responding to stress.
    Journal of Cellular Biochemistry 02/2002; 86(4):613-23. · 3.06 Impact Factor