scholarly journals BioID-based proteomic analysis of the Bid interactome identifies novel proteins involved in cell-cycle-dependent apoptotic priming

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Robert Pedley ◽  
Louise E. King ◽  
Venkatesh Mallikarjun ◽  
Pengbo Wang ◽  
Joe Swift ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Proteomic Analysis ◽  
Chemotherapeutic Agents ◽  
Novel Proteins ◽  
Antimitotic Drugs ◽  
Family Protein ◽  
Voltage Dependent ◽  
Selective Channel ◽  
Cycle Dependent

Abstract Apoptotic priming controls the commitment of cells to apoptosis by determining how close they lie to mitochondrial permeabilisation. Variations in priming are important for how both healthy and cancer cells respond to chemotherapeutic agents, but how it is dynamically coordinated by Bcl-2 proteins remains unclear. The Bcl-2 family protein Bid is phosphorylated when cells enter mitosis, increasing apoptotic priming and sensitivity to antimitotic drugs. Here, we report an unbiased proximity biotinylation (BioID) screen to identify regulators of apoptotic priming in mitosis, using Bid as bait. The screen primarily identified proteins outside of the canonical Bid interactome. Specifically, we found that voltage-dependent anion-selective channel protein 2 (VDAC2) was required for Bid phosphorylation-dependent changes in apoptotic priming during mitosis. These results highlight the importance of the wider Bcl-2 family interactome in regulating the temporal control of apoptotic priming.

scholarly journals BioID based proteomic analysis of the Bid interactome identifies novel proteins involved in cell cycle dependent apoptotic priming

2019 ◽  
Author(s):  
Robert Pedley ◽  
Louise E. King ◽  
Venkatesh Mallikarjun ◽  
Pengbo Wang ◽  
Joe Swift ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chemotherapeutic Agents ◽  
Dynamic Changes ◽  
Novel Proteins ◽  
Additional Layer ◽  
Family Protein ◽  
Voltage Dependent ◽  
Selective Channel ◽  
Control Dynamic ◽  
Cycle Dependent

AbstractApoptotic priming controls the commitment of cells to apoptosis by determining how close they lie to mitochondrial permeabilisation. Variations in priming are important for how both healthy and cancer cells respond to chemotherapeutic agents, but how this is dynamically coordinated by Bcl-2 proteins remains unclear. The Bcl-2 family protein Bid is phosphorylated when cells enter mitosis, increasing apoptotic priming and sensitivity to anti-mitotic drugs. Here we report an unbiased proximity biotinylation (BioID) screen to identify regulators of apoptotic priming in mitosis, using Bid as bait. The screen primarily identified proteins outside of the canonical Bid interactome. Specifically, we found that voltage-dependent anion-selective channel protein 2 (VDAC2) was required for Bid phosphorylation dependent changes in apoptotic priming during mitosis. Thus, we identify an additional layer of regulation upstream of known Bid interactions that control dynamic changes in apoptotic priming. These results highlight the importance of understanding the wider Bcl-2 family interactome and its role in regulating the temporal control of apoptotic priming.

scholarly journals Cell Cycle-Dependent Effects of 3,3′-Diindolylmethane on Proliferation and Apoptosis of Prostate Cancer Cells

2009 ◽  
Vol 219 (1) ◽  
pp. 94-99 ◽  
Author(s):  
Kannagi Chinnakannu ◽  
Di Chen ◽  
Yiwei Li ◽  
Zhiwei Wang ◽  
Q. Ping Dou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Proliferation And Apoptosis ◽  
Cycle Dependent

Cell-cycle-dependent expression of the large Ca2+-activated K+ channels in breast cancer cells

2004 ◽  
Vol 316 (1) ◽  
pp. 244-251 ◽  
Author(s):  
Halima Ouadid-Ahidouch ◽  
Morad Roudbaraki ◽  
Ahmed Ahidouch ◽  
Philippe Delcourt ◽  
Natalia Prevarskaya
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
K Channels ◽  
Cycle Dependent

scholarly journals Proteomic Analysis of Breast Cancer Resistance to the Anticancer Drug RH1 Reveals the Importance of Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 972
Author(s):  
Dalius Kuciauskas ◽  
Nadezda Dreize ◽  
Marija Ger ◽  
Algirdas Kaupinis ◽  
Kristijonas Zemaitis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Proteomic Analysis ◽  
Acquired Resistance ◽  
Cancer Resistance ◽  
Resistant Cells

Antitumor drug resistance remains a major challenge in cancer chemotherapy. Here we investigated the mechanism of acquired resistance to a novel anticancer agent RH1 designed to be activated in cancer cells by the NQO1 enzyme. Data show that in some cancer cells RH1 may act in an NQO1-independent way. Differential proteomic analysis of breast cancer cells with acquired resistance to RH1 revealed changes in cell energy, amino acid metabolism and G2/M cell cycle transition regulation. Analysis of phosphoproteomics and protein kinase activity by multiplexed kinase inhibitor beads showed an increase in the activity of protein kinases involved in the cell cycle and stemness regulation and downregulation of proapoptotic kinases such as JNK in RH1-resistant cells. Suppression of JNK leads to the increase of cancer cell resistance to RH1. Moreover, resistant cells have enhanced expression of stem cell factor (SCF) and stem cell markers. Inhibition of SCF receptor c-KIT resulted in the attenuation of cancer stem cell enrichment and decreased amounts of tumor-initiating cells. RH1-resistant cells also acquire resistance to conventional therapeutics while remaining susceptible to c-KIT-targeted therapy. Data show that RH1 can be useful to treat cancers in the NQO1-independent way, and targeting of the cancer stem cells might be an effective approach for combating resistance to RH1 therapy.

scholarly journals Cell Cycle-Dependent Switch of TopBP1 Functions by Cdk2 and Akt

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Kang Liu ◽  
Joshua D. Graves ◽  
Yu-Ju Lee ◽  
Fang-Tsyr Lin ◽  
Weei-Chin Lin
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cancer Cells ◽  
Cyclin A ◽  
Replication Initiation ◽  
Dna Replication Initiation ◽  
Cycle Dependent

ABSTRACT Cdk2-dependent TopBP1-treslin interaction is critical for DNA replication initiation. However, it remains unclear how this association is terminated after replication initiation is finished. Here, we demonstrate that phosphorylation of TopBP1 by Akt coincides with cyclin A activation during S and G2 phases and switches the TopBP1-interacting partner from treslin to E2F1, which results in the termination of replication initiation. Premature activation of Akt in G1 phase causes an early switch and inhibits DNA replication. TopBP1 is often overexpressed in cancer and can bypass control by Cdk2 to interact with treslin, leading to enhanced DNA replication. Consistent with this notion, reducing the levels of TopBP1 in cancer cells restores sensitivity to a Cdk2 inhibitor. Together, our study links Cdk2 and Akt pathways to the control of DNA replication through the regulation of TopBP1-treslin interaction. These data also suggest an important role for TopBP1 in driving abnormal DNA replication in cancer.

scholarly journals FHL2 Regulates Cell Cycle-Dependent and Doxorubicin-Induced p21Cip1/Waf1 Expression in Breast Cancer Cells

Cell Cycle ◽  
2007 ◽  
Vol 6 (14) ◽  
pp. 1779-1788 ◽  
Author(s):  
Bernd T. Martin ◽  
Kai Kleiber ◽  
Viktor Wixler ◽  
Monika Raab ◽  
Brigitte Zimmer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cycle Dependent

scholarly journals Jungermannenone A and B induce ROS- and cell cycle-dependent apoptosis in prostate cancer cells in vitro

2016 ◽  
Vol 37 (6) ◽  
pp. 814-824 ◽  
Author(s):  
Yan-xia Guo ◽  
Zhao-min Lin ◽  
Mei-juan Wang ◽  
Yi-wen Dong ◽  
Huan-min Niu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Cycle Dependent

scholarly journals Effect of Sterols Isolated fromMyrtillocactus geometrizanson Growth Inhibition of Colon and Breast Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Mario Augusto Bolaños-Carrillo ◽  
Jose Luis Ventura-Gallegos ◽  
Arturo David Saldivar-Jiménez ◽  
Alejandro Zentella-Dehesa ◽  
Mariano Martínez-Vázquez
Keyword(s):  
Cell Cycle ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Biological Activities ◽  
Annexin V ◽  
Parp Cleavage ◽  
Dependent Manner ◽  
Cycle Dependent ◽  
Mcf 7

Objective. To explore the effect of peniocerol and macdougallin on HCT-15 and MCF-7 cells proliferation, cell cycle, apoptosis, and PARP cleavage.Methods. HCT-15 and MCF-7 cells were treated with various concentrations of peniocerol and macdougallin (10–80 μM) during 24 or 48 h. Crystal Violet Assay was used to evaluate the inhibition effect. Cell cycle regulation was examined by a propidium iodide method. Cell apoptosis was detected through both Annexin–V FLUOS/PI double-labeled cytometry assays and Western blot was applied to assess PARP cleavage.Results. Peniocerol and macdougallin induced growth inhibition and apoptosisin vitroin a time- and dose-dependent manner. Moreover, peniocerol and macdougallin induced arrest of cell cycle-dependent manner and increased the proportion of cells in G0/G1phase. PARP cleavage in HCT-15 and MCF-7 cells was induced by treatment with peniocerol and macdougallin after 36 hours.Conclusions. Our results showed that the mechanism of cytotoxicity displayed by peniocerol and macdougallin is related to cell cycle arrest and apoptosis in both cell lines. This is a significant observation because it helps to understand the way some oxysterols isolated fromMyrtillocactus geometrizansdevelop their biological activities against cancer cells.

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