Importin β1 Protein-mediated Nuclear Localization of Death Receptor 5 (DR5) Limits DR5/Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL)-induced Cell Death of Human Tumor Cells

Kojima, Yuko; Nakayama, Masafumi; Nishina, Takashi; Nakano, Hiroyasu; Koyanagi, Makoto; Takeda, Kazuyoshi; Okumura, Ko; Yagita, Hideo

doi:10.1074/jbc.m111.309377

Cited by 63 publications

(60 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, large amounts of DR5 were localized in the nucleus in HeLa and HepG2 cells (62). We did confirm that CCB or ZER induces the increased expression of DR5 on the cell surface.…”

Section: Discussionsupporting

confidence: 74%

Role of Activating Transcription Factor 3 (ATF3) in Endoplasmic Reticulum (ER) Stress-induced Sensitization of p53-deficient Human Colon Cancer Cells to Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL)-mediated Apoptosis through Up-regulation of Death Receptor 5 (DR5) by Zerumbone and Celecoxib

Edagawa

Kawauchi

Hirata

et al. 2014

Journal of Biological Chemistry

106

View full text Add to dashboard Cite

Background: Death receptor 5 (DR5) triggers cell death upon binding to its ligand TRAIL. Results: ATF3 promotes DR5 induction and apoptotic cell death upon zerumbone or celecoxib treatment in human p53-deficient colorectal cancer cells. Conclusion: ATF3 is an essential transcription factor for p53-independent DR5 induction through the ROS-ER stress pathway. Significance: ATF3 may be a useful biomarker for TRAIL-based anticancer therapy.

show abstract

“…In addition, large amounts of DR5 were localized in the nucleus in HeLa and HepG2 cells (62). We did confirm that CCB or ZER induces the increased expression of DR5 on the cell surface.…”

Section: Discussionsupporting

confidence: 74%

Role of Activating Transcription Factor 3 (ATF3) in Endoplasmic Reticulum (ER) Stress-induced Sensitization of p53-deficient Human Colon Cancer Cells to Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL)-mediated Apoptosis through Up-regulation of Death Receptor 5 (DR5) by Zerumbone and Celecoxib

Edagawa

Kawauchi

Hirata

et al. 2014

Journal of Biological Chemistry

106

View full text Add to dashboard Cite

show abstract

“…However, little is known about the underlying molecular mechanisms. A recent study identified two nuclear localization signals in DR5 protein which mediates its nuclear localization through the nuclear import pathway by importin beta1 in Hela and HepG2 cells (32). The overexpression of DRs in cytoplasm may reflect receptor-ligand internalization, a rapid process occurring after ligand binding.…”

Section: Discussionmentioning

confidence: 99%

Mislocalization of death receptors correlates with cellular resistance to their cognate ligands in human breast cancer cells

et al. 2012

View full text Add to dashboard Cite

ABSTRACT:Multiple clinical trials are ongoing to evaluate the potential antitumor activity of human TNF variants, Fas ligand (FasL), TNF-related apoptosis inducing ligand (TRAIL) and its agonistic antibodies. These drug products act through the death receptors (DRs) TNF receptor 1 (TNFR1), Fas/CD95, DR4 (TRAIL-R1) and/or DR5 (TRAIL-R2), respectively. Therefore, characterization of the level and localization of DR expression in cancer cells is important for DR-targeted therapy. In this study, we examined the subcellular distribution of the four DRs in a panel of 10 human breast cancer cell lines by western blots and flow cytometry and 50 human breast tumors by immunohistochemistry. Despite their total protein expressions, the DRs were found to be absent on the surface of some cell lines. Consistent with this result, all four DRs were found to be mostly expressed in the cytoplasm and/or the nucleus of primary breast tumors (n=50). We further determined the growth inhibition activity (GI50) of the death ligands, recombinant human TNFα, FasL and TRAIL, and found a correlation with the subcellular localization of the corresponding DRs. These results demonstrate an aberrant expression of the death receptors in breast cancer cells, and suggest that the lack of surface DRs appears to be predictive of tumor resistance to DR-targeted therapies.

show abstract

“…Importin‐β‐mediated nuclear import of the death receptor DR5 limits the cell death of cancer cell lines. The DU145 prostate carcinoma cell line, which does not express nuclear DR5, is highly sensitive to the apoptosis‐inducing ligand TRAIL, whereas HeLa and HepG2 cells, which contain a large amount of nuclear DR5, are resistant to TRAIL . Importin‐7‐dependent nuclear import of the transcription factor Egr1, which regulates the expression of the tumor suppressor PTEN, is involved in tumor suppression.…”

Section: Imp‐βs In Pathologymentioning

confidence: 99%

Biological Significance of the Importin‐β Family‐Dependent Nucleocytoplasmic Transport Pathways

Kimura

Imamoto

2014

Traffic

133

110

View full text Add to dashboard Cite

Importin-β family proteins (Imp-βs) are nucleocytoplasmic transport receptors (NTRs) that import and export proteins and RNAs through the nuclear pores. The family consists of 14-20 members depending on the biological species, and each member transports a specific group of cargoes. Thus, the Imp-βs mediate multiple, parallel transport pathways that can be regulated separately. In fact, the spatiotemporally differential expressions and the functional regulations of Imp-βs have been reported. Additionally, the biological significance of each pathway has been characterized by linking the function of a member of Imp-βs to a cellular consequence. Connecting these concepts, the regulation of the transport pathways conceivably induces alterations in the cellular physiological states. However, few studies have linked the regulation of an importin-β family NTR to an induced cellular response and the corresponding cargoes, despite the significance of this linkage in comprehending the biological relevance of the transport pathways. This review of recent reports on the regulation and biological functions of the Imp-βs highlights the significance of the transport pathways in physiological contexts and points out the possibility that the identification of yet unknown specific cargoes will reinforce the importance of transport regulation.

show abstract

Importin β1 Protein-mediated Nuclear Localization of Death Receptor 5 (DR5) Limits DR5/Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL)-induced Cell Death of Human Tumor Cells

Cited by 63 publications

References 44 publications

Mislocalization of death receptors correlates with cellular resistance to their cognate ligands in human breast cancer cells

Biological Significance of the Importin‐β Family‐Dependent Nucleocytoplasmic Transport Pathways

Contact Info

Product

Resources

About