Browsing by Author "Beebe, Jenny"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    14-3-3σ Contributes to Radioresistance by Regulating DNA Repair and Cell Cycle via PARP1 and CHK2
    (AACR, 2017) Chen, Yifan; Li, Zhaomin; Dong, Zizheng; Beebe, Jenny; Yang, Ke; Fu, Liwu; Zhang, Jian-Ting; Department of Pharmacology and Toxicology, IU School of Medicine
    14-3-3σ has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3σ contributes to these resistances via inhibiting apoptosis and arresting cells in G2–M phase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3σ causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2–M phase following DNA-damaging treatments. We showed that 14-3-3σ contributed to ionizing radiation (IR) resistance by arresting cancer cells in G2–M phase following IR and by increasing non-homologous end joining (NHEJ) repair of the IR-induced DNA double strand breaks (DSB). The increased NHEJ repair activity was due to 14-3-3σ–mediated upregulation of PARP1 expression that promoted the recruitment of DNA-PKcs to the DNA damage sites for repair of DSBs. On the other hand, the increased G2–M arrest following IR was due to 14-3-3σ–induced Chk2 expression. Implications: These findings reveal an important molecular basis of 14-3-3σ function in cancer cell resistance to chemo/radiation therapy and in poor prognosis of human cancers.
  • Thumbnail Image
    Item
    Corrigendum: eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation
    (Frontiers Media, 2021-01-07) Tumia, Rima; Wang, Chao J.; Dong, Tianhan; Ma, Shijie; Beebe, Jenny; Chen, Juan; Dong, Zizheng; Liu, Jing-Yuan; Zhang, Jian-Ting; Pharmacology and Toxicology, School of Medicine
    [This corrects the article DOI: 10.3389/fcell.2020.00753.].
  • Thumbnail Image
    Item
    eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation
    (Frontiers, 2020-08-19) Tumia, Rima; Wang, Chao J.; Dong, Tianhan; Ma, Shijie; Beebe, Jenny; Chen, Juan; Dong, Zizheng; Liu, Jing-Yuan; Zhang, Jian-Ting; Pharmacology and Toxicology, School of Medicine
    Translation initiation in protein synthesis regulated by eukaryotic initiation factors (eIFs) is a crucial step in controlling gene expression. eIF3a has been shown to regulate protein synthesis and cellular response to treatments by anticancer agents including cisplatin by regulating nucleotide excision repair. In this study, we tested the hypothesis that eIF3a regulates the synthesis of proteins important for the repair of double-strand DNA breaks induced by ionizing radiation (IR). We found that eIF3a upregulation sensitized cellular response to IR while its downregulation caused resistance to IR. eIF3a increases IR-induced DNA damages and decreases non-homologous end joining (NHEJ) activity by suppressing the synthesis of NHEJ repair proteins. Furthermore, analysis of existing patient database shows that eIF3a expression associates with better overall survival of breast, gastric, lung, and ovarian cancer patients. These findings together suggest that eIF3a plays an important role in cellular response to DNA-damaging treatments by regulating the synthesis of DNA repair proteins and, thus, eIIF3a likely contributes to the outcome of cancer patients treated with DNA-damaging strategies including IR.
  • Thumbnail Image
    Item
    Two decades of research in discovery of anticancer drugs targeting STAT3, how close are we?
    (Elsevier, 2018) Beebe, Jenny; Liu, Jing-Yuan; Zhang, Jian-Ting; Pharmacology and Toxicology, School of Medicine
    Signal transducer and activator of transcription 3 (STAT3) controls many biological processes including differentiation, survival, proliferation, and angiogenesis. In normal healthy cells, STAT3 is tightly regulated to maintain a momentary active state. However, aberrant or constitutively activated STAT3 has been observed in many different cancers and constitutively activated STAT3 has been shown to associate with poor prognosis and tumor progression. For this reason, STAT3 has been studied as a possible target in the treatment of many different types of cancers. However, despite decades of research, a FDA-approved STAT3 inhibitor has yet to emerge. In this review, we will analyze past studies targeting STAT3 for drug discovery, understand possible causes of failure in these studies, and provide potential insights for future efforts to overcome these roadblocks.