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cancer

  • Proteasomal Regulation of Mammalian SPT16 in Controlling Transcription
    Research Article
    Proteasomal Regulation of Mammalian SPT16 in Controlling Transcription

    FACT (facilitates chromatin transcription), an essential and evolutionarily conserved heterodimer from yeast to humans, controls transcription and is found to be upregulated in various cancers. However, the basis for such upregulation is not clearly understood.

    Amala Kaja, Abhinav Adhikari, Saswati Karmakar, Wanwei Zhang, Gerson Rothschild, Uttiya Basu, Surinder K. Batra, Judith K. Davie, Sukesh R. Bhaumik
  • A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective
    Minireview
    A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective

    SHOC2 is a prototypical leucine-rich repeat protein that promotes downstream receptor tyrosine kinase (RTK)/RAS signaling and plays important roles in several cellular and developmental processes. Gain-of-function germ line mutations of SHOC2 drive the RASopathy Noonan-like syndrome, and SHOC2 mediates adaptive resistance to mitogen-activated protein kinase (MAPK) inhibitors.

    Jason J. Kwon, William C. Hahn
  • NRF2-Dependent Bioactivation of Mitomycin C as a Novel Strategy To Target KEAP1-NRF2 Pathway Activation in Human Cancer
    Research Article
    NRF2-Dependent Bioactivation of Mitomycin C as a Novel Strategy To Target KEAP1-NRF2 Pathway Activation in Human Cancer

    Activating mutations in the KEAP1-NRF2 pathway are found in approximately 25% of lung tumors, where the hijacking of NRF2’s cytoprotective functions results in aggressive tumor growth, chemoresistance, and a poor prognosis for patients. There are currently no approved drugs which target aberrant NRF2 activation, which means that there is an urgent clinical need to target this orphan oncogenic pathway in human tumors. In this study, we...

    Liam Baird, Masayuki Yamamoto
  • Geldanamycin-Derived HSP90 Inhibitors Are Synthetic Lethal with NRF2
    Research Article | Spotlight
    Geldanamycin-Derived HSP90 Inhibitors Are Synthetic Lethal with NRF2

    Activating mutations in KEAP1-NRF2 are frequently found in tumors of the lung, esophagus, and liver, where they are associated with aggressive growth, resistance to cancer therapies, and low overall survival. Despite the fact that NRF2 is a validated driver of tumorigenesis and chemotherapeutic resistance, there are currently no approved drugs which can inhibit its activity. Therefore, there is an urgent clinical need to identify NRF2-...

    Liam Baird, Takafumi Suzuki, Yushi Takahashi, Eiji Hishinuma, Daisuke Saigusa, Masayuki Yamamoto
  • Lysine Demethylase KDM6A in Differentiation, Development, and Cancer
    Minireview
    Lysine Demethylase KDM6A in Differentiation, Development, and Cancer

    Lysine demethylase 6A (KDM6A), also known as UTX, belongs to the KDM6 family of histone H3 lysine 27 (H3K27) demethylases, which also includes UTY and KDM6B (JMJD3). The KDM6A protein contains six tetratricopeptide repeat (TPR) domains and an enzymatic Jumonji C (JmjC) domain that catalyzes the removal of di- and trimethylation on H3K27. KDM6A physically associates with histone H3 lysine 4 monomethyltransferases MLL3 (KMT2C) and MLL4 (...

    Nhien Tran, Aaron Broun, Kai Ge
  • Histone Acetyltransferase MOF Orchestrates Outcomes at the Crossroad of Oncogenesis, DNA Damage Response, Proliferation, and Stem Cell Development
    Minireview
    Histone Acetyltransferase MOF Orchestrates Outcomes at the Crossroad of Oncogenesis, DNA Damage Response, Proliferation, and Stem Cell Development

    The DNA and protein complex known as chromatin is subject to posttranslational modifications (PTMs) that regulate cellular functions such that PTM dysregulation can lead to disease, including cancer. One critical PTM is acetylation/deacetylation, which is being investigated as a means to develop targeted cancer therapies. The histone acetyltransferase (HAT) family of proteins performs histone acetylation. In humans, MOF (hMOF), a member...

    Mayank Singh, Albino Bacolla, Shilpi Chaudhary, Clayton R. Hunt, Shruti Pandita, Ravi Chauhan, Ashna Gupta, John A. Tainer, Tej K. Pandita
  • AKT Regulates Mitotic Progression of Mammalian Cells by Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation
    Research Article
    AKT Regulates Mitotic Progression of Mammalian Cells by Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation

    Microtubule-associated serine/threonine kinase like (MASTL), also known as Greatwall (Gwl) kinase, has an important role in the regulation of mitosis. By inhibiting protein phosphatase 2A (PP2A), it plays a crucial role in activating one of the most important mitotic kinases, known as cyclin-dependent kinase 1 (CDK1). MASTL has been seen to be upregulated in various types of cancers and is also involved in tumor recurrence. It is...

    Irfana Reshi, Misbah Un Nisa, Umer Farooq, Syed Qaaifah Gillani, Sameer Ahmed Bhat, Zarka Sarwar, Nusrat Nabi, Khalid Majid Fazili, Shaida Andrabi
  • Bugs as Cancer Drugs: Challenges and Opportunities
    Commentary
    Bugs as Cancer Drugs: Challenges and Opportunities

    The first nonsurgical cancer therapy was bacterial therapy introduced in 1891 to treat solid tumors. Because in many cases it was harmful and ineffective, and with the emergence of radiotherapy and chemotherapy, bacterial therapy was discontinued.

    Phillip J. Daschner, Avraham Rasooly, Jeffrey D. White
  • Uncoupling the Senescence-Associated Secretory Phenotype from Cell Cycle Exit via Interleukin-1 Inactivation Unveils Its Protumorigenic Role
    Research Article | Spotlight
    Uncoupling the Senescence-Associated Secretory Phenotype from Cell Cycle Exit via Interleukin-1 Inactivation Unveils Its Protumorigenic Role

    Cellular senescence has emerged as a potent tumor suppressor mechanism in numerous human neoplasias. Senescent cells secrete a distinct set of factors, collectively termed the senescence-associated secretory phenotype (SASP), which has been postulated to carry both pro- and antitumorigenic properties depending on tissue context.

    Lena Lau, Angelo Porciuncula, Alex Yu, Yoichiro Iwakura, Gregory David
  • Research Article
    Depletion of Mediator Kinase Module Subunits Represses Superenhancer-Associated Genes in Colon Cancer Cells
    Emilia Kuuluvainen, Eva Domènech-Moreno, Elina H. Niemelä, Tomi P. Mäkelä

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