Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia

@article{Ohayon2016CytoplasmicPC,
  title={Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia},
  author={Delphine Ohayon and Alessia De Chiara and Nicolas Chapuis and C{\'e}line Candalh and Julie Mocek and Jean-Antoine Ribeil and Lamya Haddaoui and Norbert Ifrah and Olivier Hermine and Fr{\'e}d{\'e}ric Bouillaud and Philippe Frachet and Didier Bouscary and V{\'e}ronique Witko-Sarsat},
  journal={Scientific Reports},
  year={2016},
  volume={6}
}
Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60… 
Targeting Proliferating Cell Nuclear Antigen (PCNA) as an Effective Strategy to Inhibit Tumor Cell Proliferation.
TLDR
The status of the art in the development of agents targeting PCNA is described and their application in different types of tumor cell lines and in animal model systems is discussed.
PCNA has specific functions in regulation of metabolism in haematological cells
TLDR
Impaired PCNA’s cytosolic scaffold functions led to massive changes in cellular signaling, and most strikingly, a strong reduction in glycolytic metabolite and nucleoside phosphate pools in haematological cancer cells, indicating a special role of PCNA in regulation of metabolism in cells of haem atological origin.
Genetic Expression Screening of Arsenic Trioxide-Induced Cytotoxicity in KG-1a Cells Based on Bioinformatics Technology
TLDR
This study suggests that ATO not only inhibits the expression of MYC, PCNA, and MCM7 but also leads to cell cycle arrest and apoptosis in KG-1a cells, which provided reliable clues for improving the ATO efficacy in AML.
Cytoplasmic PCNA is located in the actin belt and involved in osteoclast differentiation
TLDR
It is shown that PCNA is translocated from nucleus to cytoplasm during the RANKL-induced osteoclast differentiation, and localized in the actin belt of mature osteoporosis, demonstrating the critical role of cy toplasmic PCNA during the process of osteOClast differentiation.
The role of PCNA as a scaffold protein in cellular signaling is functionally conserved between yeast and humans
TLDR
The results suggest that the interactions between APIM‐containing signaling proteins and PCNA during the DNA damage response is evolutionary conserved between yeast and mammals and that PCNA has a role in cellular signaling also in yeast.
Inhibition of the NKp44-PCNA Immune Checkpoint Using a mAb to PCNA
TLDR
It is shown here that antitumor responses by natural killer (NK) cells can be enhanced by a checkpoint-blocking mAb, 14-25-9, which was developed against proliferating cell nuclear antigen (PCNA), a ligand for NK-cell protein NKp44.
Interfering cellular lactate homeostasis overcomes Taxol resistance of breast cancer cells through the microRNA-124-mediated lactate transporter (MCT1) inhibition
TLDR
This study reveals a possible role of miRNA-214-mediated Taxol resistance, contributing to identify novel therapeutic targets against chemoresistant breast cancers.
Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy
  • C. Heske
  • Biology
    Frontiers in Oncology
  • 2019
TLDR
This review highlights the recent findings describing the effects of NAMPT inhibitors on the non-metabolic functions of malignant cells, with a focus on how this information can be leveraged clinically.
...
...

References

SHOWING 1-10 OF 69 REFERENCES
Nuclear-to-cytoplasmic Relocalization of the Proliferating Cell Nuclear Antigen (PCNA) during Differentiation Involves a Chromosome Region Maintenance 1 (CRM1)-dependent Export and Is a Prerequisite for PCNA Antiapoptotic Activity in Mature Neutrophils*
TLDR
It is shown that leptomycin B, an inhibitor of the chromosome region maintenance 1 (CRM1) exportin, inhibited PCNA relocalization during granulocytic differentiation of HL-60 and NB4 promyelocytic cell lines and of human CD34+ primary cells.
Proliferating cell nuclear antigen in neutrophil fate
TLDR
The neutrophil emerges as a unique and powerful cellular model to unravel the basic mechanisms governing the cell cycle‐independent functions of PCNA and should be considered as a leader of the pack.
Targeting cytosolic proliferating cell nuclear antigen in neutrophil-dominated inflammation
TLDR
Through an intimate comprehension of the cytosolic PCNA scaffold based on nuclear PCNA knowledge, novel pathways regulating neutrophil survival can be unraveled and innovative agents can be developed to dampen inflammation where it proves detrimental.
Targeting Proliferating Cell Nuclear Antigen and Its Protein Interactions Induces Apoptosis in Multiple Myeloma Cells
TLDR
A cell-penetrating APIM-containing peptide, ATX-101, is designed and shown to have anti-myeloma activity and induced apoptosis in multiple myeloma cell lines and primary cancer cells, while bone marrow stromal cells and primary healthy lymphocytes were much less sensitive.
Characterization of cytosolic proliferating cell nuclear antigen (PCNA) in neutrophils: antiapoptotic role of the monomer
TLDR
The molecular basis through which cytoplasmic PCNA exerts its antiapoptotic activity in mature neutrophils may, at least in part, be independent of the trimeric conformation.
Inflammation-associated Cell Cycle–independent Block of Apoptosis by Survivin in Terminally Differentiated Neutrophils
TLDR
Together, the findings demonstrate that survivin plays distinct and independent roles in the maintenance of the G2-M checkpoint and in apoptosis control, and its overexpression is not restricted to proliferating cells.
Common alterations in gene expression and increased proliferation in recurrent acute myeloid leukemia
TLDR
Expression profiling in blasts from untreated AML and relapse showed that recurrent AML is commonly associated with the mRNA expression changes in a set of 58 genes, and enhanced activation of the RAF/MEK/ERK cascade was found as mRNAs of MKP-1, c-jun,c-fos, and egr-1 were significantly increased at relapse.
Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia.
TLDR
It is shown that glutamine removal inhibits mTORC1 and induces apoptosis in AML cells, and that l-ases upregulate glutamine synthase expression in leukemic cells and that a GS knockdown enhances l-ase-induced apoptotic response in someAML cells.
Prognostic impact and targeting of CRM1 in acute myeloid leukemia.
TLDR
Data suggest that CRM1 exerts an antiapoptotic function and is highly prognostic in AML, and a novel combinatorial approach is proposed aimed at maximal activation of p53-mediated apoptosis by concomitant MDM2 andCRM1 inhibition.
Peculiarities of cell death mechanisms in neutrophils
TLDR
The current and emerging models of neutrophil cell death mechanisms are reviewed with a focus on neutrophils peculiarities, including mitochondrial death pathway, and pharmacological intervention of inflammation.
...
...