Ubiquitin-like (UBX)-domain-containing protein, UBXN2A, promotes cell death by interfering with the p53-Mortalin interactions in colon cancer cells

@article{Sane2014UbiquitinlikeP,
  title={Ubiquitin-like (UBX)-domain-containing protein, UBXN2A, promotes cell death by interfering with the p53-Mortalin interactions in colon cancer cells},
  author={S. Sane and A. Abdullah and D. Boudreau and R. Autenried and B. K. Gupta and X. Wang and H. Wang and E. H. Schlenker and D. Zhang and C. Telleria and L. Huang and S. Chauhan and K. Rezvani},
  journal={Cell Death \& Disease},
  year={2014},
  volume={5}
}
Mortalin (mot-2) induces inactivation of the tumor suppressor p53’s transcriptional and apoptotic functions by cytoplasmic sequestration of p53 in select cancers. The mot-2-dependent cytoprotective function enables cancer cells to support malignant transformation. Abrogating the p53-mot-2 interaction can control or slow down the growth of cancer cells. In this study, we report the discovery of a ubiquitin-like (UBX)-domain-containing protein, UBXN2A, which binds to mot-2 and consequently… Expand
Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy
TLDR
Details are provided into the mechanistic role of UBXN2A as a potent mortalin inhibitor and as a potential chemotherapy sensitizer for clinical application and how three amino acids within the substrate-binding domain of mortalin are crucial for UBxN 2A binding to mortalin. Expand
Nucleocytoplasmic Translocation of UBXN 2 A Is Required for Apoptosis during DNA Damage Stresses in Colon Cancer Cells
The subcellular localization, expression level, and activity of anti-cancer proteins alter in response to intrinsic and extrinsic cellular stresses to reverse tumor progression. The purpose of thisExpand
UBXN2A enhances CHIP‐mediated proteasomal degradation of oncoprotein mortalin‐2 in cancer cells
TLDR
The existence of a multiprotein complex containing UBXN2A, CHIP, and mot‐2 suggests a synergistic tumor suppressor activity of UBxN 2A and CHIP in mot‐ 2‐enriched tumors, and validates the UB XN2a‐CHIP axis as a novel and potential therapeutic target in CRC. Expand
UBXD Proteins: A Family of Proteins with Diverse Functions in Cancer
  • K. Rezvani
  • Biology, Medicine
  • International journal of molecular sciences
  • 2016
TLDR
This review covers recent advances that elucidate the therapeutic potential of selected members of the UBXD family that can contribute to tumor growth. Expand
Essential Roles of E3 Ubiquitin Ligases in p53 Regulation
  • S. Sane, K. Rezvani
  • Chemistry, Medicine
  • International journal of molecular sciences
  • 2017
TLDR
This review provides a comprehensive understanding of p53 regulation by selective E3 ubiquitin ligases and their potential to be considered as a new class of biomarkers and therapeutic targets in diverse types of cancers. Expand
Molecular dynamics-based identification of novel natural mortalin–p53 abrogators as anticancer agents
TLDR
This study used structure-based approach to target the p53-binding domain of mortalin in order to prevent mortalin–p53 complex formation and observed that residues Tyr196, Asn198, Val264 and Thr267 were involved in intermolecular interactions in both the simulated ligand-bound complexes, and thus, these residues may have a paramount role in stabilizing the binding of the ligands with the protein. Expand
A plant alkaloid, veratridine, potentiates cancer chemosensitivity by UBXN2A-dependent inhibition of an oncoprotein, mortalin-2
TLDR
The VTD-dependent expression of UBXN2A is a potential candidate for designing novel strategies for colon cancer treatment, and VTD or its modified analogs offer a valuable adjuvant chemotherapy strategy to improve the efficacy of 5-FU-based chemotherapy for Colon cancer patients harboring WT-p53. Expand
Stress chaperone mortalin contributes to epithelial-mesenchymal transition and cancer metastasis.
TLDR
A role for mortalin in the induction of EMT is supported, prompting further investigation of its therapeutic value in metastatic disease models and consistent with high mortalin expression in various human tumors and cell lines. Expand
Fucoxanthin induces growth arrest and apoptosis in human bladder cancer T24 cells by up-regulation of p21 and down-regulation of mortalin.
TLDR
MTT analysis results demonstrated that the anti-cancer activity of fucoxanthin on T24 cells was associated with cell cycle arrest at G0/G1 phase by up-regulation of p21 at low doses and apoptosis via decrease in the expression level of mortalin, which is a stress regulator and a member of heat shock protein 70. Expand
p73 promotes glioblastoma cell invasion by directly activating POSTN (periostin) expression
TLDR
Results support a novel role of TAp73 in controlling glioblastoma cell invasion by regulating the expression of the matricellular protein POSTN. Expand
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TLDR
A novel mechanism of p53 inactivation by mot-2 protein is demonstrated, supported by the down-regulation of p 53-responsive genes p21WAF-1 andmdm-2 in mot-1-transfected cells only and an abrogation of nuclear translocation of wild-type p53. Expand
Ubiquitin-Associated (UBA) Domain in Human Fas Associated Factor 1 Inhibits Tumor Formation by Promoting Hsp70 Degradation
TLDR
HFAF1 inhibits tumor formation by increasing the degradation of Hsp70 mediated via its UBA domain, and mutating the UBAdomain (I41N), as well as knocking down hFAF 1 with specific RNAi, abolishs its ability to increase the proteasomal degradation ofHsp70. Expand
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TLDR
A molecular interaction basis that could be used for screening and development of anticancer drugs with low toxicity to normal cells is established and accurate knowledge of the 3D structure of mortalin would further enhance the potential of such analyses to understand the molecular basis ofmortalin biology and mortalin based cancer therapy. Expand
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
The characteristic cytoplasmic sequestration of p53 by the heat shock protein mortalin in human colorectal adenocarcinoma cell lines, as is the case for other cancers, such as glioblastomas and hepatocellular carcinomas, is revealed. Expand
UBXD7 Binds Multiple Ubiquitin Ligases and Implicates p97 in HIF1α Turnover
TLDR
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