scholarly journals Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions

2019 ◽  
Vol 20 (9) ◽  
pp. 2304 ◽  
Author(s):  
Sachiko Matsuhashi ◽  
M. Manirujjaman ◽  
Hiroshi Hamajima ◽  
Iwata Ozaki
Keyword(s):  
Tumor Suppressor ◽  
Ubiquitin Ligase ◽  
Gene Mutations ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Control Mechanisms ◽  
Inflammatory Conditions ◽  
Binding Partners ◽  
Factor Eif4a ◽  
Pdcd4 Protein

PDCD4 is a novel tumor suppressor to show multi-functions inhibiting cell growth, tumor invasion, metastasis, and inducing apoptosis. PDCD4 protein binds to the translation initiation factor eIF4A, some transcription factors, and many other factors and modulates the function of the binding partners. PDCD4 downregulation stimulates and PDCD4 upregulation inhibits the TPA-induced transformation of cells. However, PDCD4 gene mutations have not been found in tumor cells but gene expression was post transcriptionally downregulated by micro environmental factors such as growth factors and interleukins. In this review, we focus on the suppression mechanisms of PDCD4 protein that is induced by the tumor promotors EGF and TPA, and in the inflammatory conditions. PDCD4-protein is phosphorylated at 2 serines in the SCFβTRCP ubiquitin ligase binding sequences via EGF and/or TPA induced signaling pathway, ubiquitinated, by the ubiquitin ligase and degraded in the proteasome system. The PDCD4 protein synthesis is inhibited by microRNAs including miR21.

scholarly journals Proteins of the Nucleolus of Dictyostelium discoideum: Nucleolar Compartmentalization, Targeting Sequences, Protein Translocations and Binding Partners

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 167 ◽  
Author(s):  
Danton O’Day
Keyword(s):  
Cell Cycle ◽  
Dictyostelium Discoideum ◽  
Cell Cycle Checkpoint ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Tumour Necrosis Factor Receptor ◽  
Cancer Type ◽  
Binding Partners ◽  
Nucleolar Proteins ◽  
C Terminus

The nucleoli of Dictyostelium discoideum have a comparatively unique, non-canonical, localization adjacent to the inner nuclear membrane. The verified nucleolar proteins of this eukaryotic microbe are detailed while other potential proteins are introduced. Heat shock protein 32 (Hsp32), eukaryotic translation initiation factor 6 (eIF6), and tumour necrosis factor receptor-associated protein 1 (TRAP1) are essential for cell survival. NumA1, a breast cancer type 1 susceptibility protein-C Terminus domain-containing protein linked to cell cycle, functions in the regulation of nuclear number. The cell cycle checkpoint kinase 2 homologue forkhead-associated kinase A (FhkA) and BRG1-associated factor 60a homologue Snf12 are also discussed. While nucleoli appear homogeneous ultrastructurally, evidence for nucleolar subcompartments exists. Nucleolar localization sequences (NoLS) have been defined that target proteins to either the general nucleolar area or to a specific intranucleolar domain. Protein translocations during mitosis are protein-specific and support the multiple functions of the Dictyostelium nucleolus. To enrich the picture, binding partners of NumA1, the most well-characterized nucleolar protein, are examined: nucleolar Ca2+-binding protein 4a (CBP4a), nuclear puromycin-sensitive aminopeptidase A (PsaA) and Snf12. The role of Dictyostelium as a model for understanding the contribution of nucleolar proteins to various diseases and cellular stress is discussed throughout the review.

scholarly journals Development of Novel Anticancer Agents that Target Prohibitins and the Translation Initiation Factor eIF4A

2015 ◽  
Vol 26 ◽  
pp. ii25
Author(s):  
L. Désaubry ◽  
Q. Zhao ◽  
C. Basmadjian ◽  
F. Thuaud ◽  
N. Ribeiro ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Anticancer Agents ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Factor Eif4a

scholarly journals The E3 Ubiquitin Ligase ARIH1 Protects against Genotoxic Stress by Initiating a 4EHP-Mediated mRNA Translation Arrest

2015 ◽  
Vol 35 (7) ◽  
pp. 1254-1268 ◽  
Author(s):  
Louise von Stechow ◽  
Dimitris Typas ◽  
Jordi Carreras Puigvert ◽  
Laurens Oort ◽  
Ramakrishnaiah Siddappa ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Mrna Translation ◽  
Genotoxic Stress ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Dependent Manner ◽  
Translation Arrest

DNA damage response signaling is crucial for genome maintenance in all organisms and is corrupted in cancer. In an RNA interference (RNAi) screen for (de)ubiquitinases and sumoylases modulating the apoptotic response of embryonic stem (ES) cells to DNA damage, we identified the E3 ubiquitin ligase/ISGylase, ariadne homologue 1 (ARIH1). Silencing ARIH1 sensitized ES and cancer cells to genotoxic compounds and ionizing radiation, irrespective of their p53 or caspase-3 status. Expression of wild-type but not ubiquitinase-defective ARIH1 constructs prevented sensitization caused by ARIH1 knockdown. ARIH1 protein abundance increased after DNA damage through attenuation of proteasomal degradation that required ATM signaling. Accumulated ARIH1 associated with 4EHP, and in turn, this competitive inhibitor of the eukaryotic translation initiation factor 4E (eIF4E) underwent increased nondegradative ubiquitination upon DNA damage. Genotoxic stress led to an enrichment of ARIH1 in perinuclear, ribosome-containing regions and triggered 4EHP association with the mRNA 5′ cap as well as mRNA translation arrest in an ARIH1-dependent manner. Finally, restoration of DNA damage-induced translation arrest in ARIH1-depleted cells by means of an eIF2 inhibitor was sufficient to reinstate resistance to genotoxic stress. These findings identify ARIH1 as a potent mediator of DNA damage-induced translation arrest that protects stem and cancer cells against genotoxic stress.

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