LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 48

Search options

  1. Article: Mutant

    Canar, Jorge / Manandhar-Sasaki, Prima / Bargonetti, Jill

    Cancers

    2022  Volume 14, Issue 19

    Abstract: ... ...

    Abstract The
    Language English
    Publishing date 2022-10-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14194929
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article: A CANCER PERSISTENT DNA REPAIR CIRCUIT DRIVEN BY MDM2, MDM4 (MDMX), AND MUTANT P53 FOR RECRUITMENT OF MDC1 AND 53BP1 TO CHROMATIN.

    Ellison, Viola / Polotskaia, Alla / Xiao, Gu / Leybengrub, Pamella / Qiu, Weigang / Lee, Rusia / Hendrickson, Ronald / Hu, Wenwei / Bargonetti, Jill

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The influence of the metastasis promoting proteins mutant p53 (mtp53) and MDM2 ... ...

    Abstract The influence of the metastasis promoting proteins mutant p53 (mtp53) and MDM2 on
    Language English
    Publishing date 2024-01-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.20.576487
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Gain-of-function mutant p53: history and speculation.

    Bargonetti, Jill / Prives, Carol

    Journal of molecular cell biology

    2019  Volume 11, Issue 7, Page(s) 605–609

    MeSH term(s) Animals ; Gain of Function Mutation ; History, 20th Century ; History, 21st Century ; Humans ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/history ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances TP53 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2019-07-05
    Publishing country United States
    Document type Historical Article ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2500949-7
    ISSN 1759-4685 ; 1674-2788
    ISSN (online) 1759-4685
    ISSN 1674-2788
    DOI 10.1093/jmcb/mjz067
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome.

    Wang, Jianming / Chang, Chun-Yuan / Yang, Xue / Zhou, Fan / Liu, Juan / Bargonetti, Jill / Zhang, Lanjing / Xie, Ping / Feng, Zhaohui / Hu, Wenwei

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 137

    Abstract: Radiation-induced gastrointestinal syndrome is a major complication and limiting factor for radiotherapy. Tumor suppressor p53 has a protective role in radiation-induced gastrointestinal toxicity. However, its underlying mechanism remains unclear. Here ... ...

    Abstract Radiation-induced gastrointestinal syndrome is a major complication and limiting factor for radiotherapy. Tumor suppressor p53 has a protective role in radiation-induced gastrointestinal toxicity. However, its underlying mechanism remains unclear. Here we report that regulating the IL12-p40/MHC class II signaling pathway is a critical mechanism by which p53 protects against radiation-induced gastrointestinal syndrome. p53 inhibits the expression of inflammatory cytokine IL12-p40, which in turn suppresses the expression of MHC class II on intestinal epithelial cells to suppress T cell activation and inflammation post-irradiation that causes intestinal stem cell damage. Anti-IL12-p40 neutralizing antibody inhibits inflammation and rescues the defects in intestinal epithelial regeneration post-irradiation in p53-deficient mice and prolongs mouse survival. These results uncover that the IL12-p40/MHC class II signaling mediates the essential role of p53 in ensuring intestinal stem cell function and proper immune reaction in response to radiation to protect mucosal epithelium, and suggest a potential therapeutic strategy to protect against radiation-induced gastrointestinal syndrome.
    MeSH term(s) Animals ; Mice ; Tumor Suppressor Protein p53/metabolism ; Apoptosis/radiation effects ; Intestinal Mucosa/metabolism ; Radiation Injuries/metabolism ; Inflammation/metabolism ; Interleukin-12/metabolism
    Chemical Substances Tumor Suppressor Protein p53 ; Interleukin-12 (187348-17-0)
    Language English
    Publishing date 2024-01-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-44390-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Contemplations on MDMX (MDM4) driving triple negative breast cancer circulating tumor cells and metastasis.

    Gao, Chong / Xiao, Gu / Bargonetti, Jill

    Oncotarget

    2019  Volume 10, Issue 49, Page(s) 5007–5010

    Abstract: MDMX (MDM4) is emerging as an important breast cancer (BC) biomarker, and oncoprotein, that can be targeted in combination with its well-known family member MDM2. While MDM2 has previously been implicated in driving BC metastasis, information about the ... ...

    Abstract MDMX (MDM4) is emerging as an important breast cancer (BC) biomarker, and oncoprotein, that can be targeted in combination with its well-known family member MDM2. While MDM2 has previously been implicated in driving BC metastasis, information about the role of MDMX in driving circulating tumor cells (CTCs) and BC metastasis is lacking. BCs often have alterations of MDM2, MDMX, and mutant p53 (mtp53). Therefore, the role of MDM2 and MDMX in the context of mtp53 in BCs requires further clarification. Our group has recently reported that triple negative breast cancer (TNBC) metastasis is dependent on both MDM2 and MDMX, and depleting MDM2 results in increased MDMX, but depleting MDMX does not cause an increase in MDM2. In the context of human TNBC expressing mtp53 in an orthotopic mouse model the down-regulation of MDMX virtually cleared CTCs from the blood. Contemplations, using the available literature, suggest that disrupting the stability and/or function of MDMX protein (and its downstream targets), in the context of mtp53 expressing BCs, might be beneficial for patient survival. It remains to be determined if blocking mtp53-MDMX pathways can inhibit early stage TNBC and eliminate CTCs that have the potential to form metastatic lesions.
    Language English
    Publishing date 2019-08-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.27134
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: The C-terminus of Gain-of-Function Mutant p53 R273H Is Required for Association with PARP1 and Poly-ADP-Ribose.

    Lundine, Devon / Annor, George K / Chavez, Valery / Maimos, Styliana / Syed, Zafar / Jiang, Shuhong / Ellison, Viola / Bargonetti, Jill

    Molecular cancer research : MCR

    2022  Volume 20, Issue 12, Page(s) 1799–1810

    Abstract: The TP53 gene is mutated in 80% of triple-negative breast cancers. Cells that harbor the hot-spot p53 gene mutation R273H produce an oncogenic mutant p53 (mtp53) that enhances cell proliferative and metastatic properties. The enhanced activities of mtp53 ...

    Abstract The TP53 gene is mutated in 80% of triple-negative breast cancers. Cells that harbor the hot-spot p53 gene mutation R273H produce an oncogenic mutant p53 (mtp53) that enhances cell proliferative and metastatic properties. The enhanced activities of mtp53 are collectively referred to as gain-of-function (GOF), and may include transcription-independent chromatin-based activities shared with wild-type p53 (wtp53) such as association with replicating DNA and DNA replication associated proteins like PARP1. However, how mtp53 upregulates cell proliferation is not well understood. wtp53 interacts with PARP1 using a portion of its C-terminus. The wtp53 oligomerization and far C-terminal domain (CTD) located within the C-terminus constitute putative GOF-associated domains, because mtp53 R273H expressing breast cancer cells lacking both domains manifest slow proliferation phenotypes. We addressed if the C-terminal region of mtp53 R273H is important for chromatin interaction and breast cancer cell proliferation using CRISPR-Cas9 mutated MDA-MB-468 cells endogenously expressing mtp53 R273H C-terminal deleted isoforms (R273HΔ381-388 and R273HΔ347-393). The mtp53 R273HΔ347-393 lacks the CTD and a portion of the oligomerization domain. We observed that cells harboring mtp53 R273HΔ347-393 (compared with mtp53 R273H full-length) manifest a significant reduction in chromatin, PARP1, poly-ADP-ribose (PAR), and replicating DNA binding. These cells also exhibited impaired response to hydroxyurea replicative stress, decreased sensitivity to the PARP-trapping drug combination temozolomide-talazoparib, and increased phosphorylated 53BP1 foci, suggesting reduced Okazaki fragment processing.
    Implications: The C-terminal region of mtp53 confers GOF activity that mediates mtp53-PARP1 and PAR interactions assisting DNA replication, thus implicating new biomarkers for PARP inhibitor therapy.
    MeSH term(s) Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Poly Adenosine Diphosphate Ribose ; Genes, p53 ; Gain of Function Mutation ; Poly (ADP-Ribose) Polymerase-1 ; Chromatin
    Chemical Substances Tumor Suppressor Protein p53 ; Poly Adenosine Diphosphate Ribose (26656-46-2) ; Poly (ADP-Ribose) Polymerase-1 (EC 2.4.2.30) ; Chromatin
    Language English
    Publishing date 2022-09-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2098788-2
    ISSN 1557-3125 ; 1541-7786
    ISSN (online) 1557-3125
    ISSN 1541-7786
    DOI 10.1158/1541-7786.MCR-22-0133
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5744: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article: MDM2-C Functions as an E3 Ubiquitin Ligase.

    Kim, Jun Yeob / Lee, Rusia / Xiao, Gu / Forbes, Dominique / Bargonetti, Jill

    Cancer management and research

    2020  Volume 12, Page(s) 7715–7724

    Abstract: Background: Mouse double minute 2 (MDM2) is an E3 ubiquitin ligase that is over-expressed in many cancers and regulates target proteins through ubiquitination. Full-length MDM2 (MDM2-FL) is best known for targeting wild-type p53 for degradation by the ... ...

    Abstract Background: Mouse double minute 2 (MDM2) is an E3 ubiquitin ligase that is over-expressed in many cancers and regulates target proteins through ubiquitination. Full-length MDM2 (MDM2-FL) is best known for targeting wild-type p53 for degradation by the proteasome, but the functions of the many splice variants of MDM2 are under-explored. The three well-studied alternative MDM2 isoforms are MDM2-A/ALT2, MDM2-B/ALT1, and MDM2-C/ALT3. MDM2-A and MDM2-B are capable of down-regulating MDM2-FL activity and have transforming activity in cancers with mutant p53. The MDM2 isoform MDM2-C is over-expressed in breast cancer and correlates with decreased survival in the context of mutant p53 expression. Therefore, MDM2-C requires further study to determine if it has biochemical activities similar to MDM2-FL. Hypothesis: We hypothesized that like MDM2-FL, the MDM2-C isoform (lacking exons 5-9 and containing a full C-terminal RING finger sequence) would maintain E3 ubiquitin ligase activity.
    Materials and methods: In order to explore the biochemical function of MDM2-C, we used an in vitro ubiquitination assay and a glutaraldehyde cross-linking assay.
    Results: Here we report, for the first time, that MDM2-C has E3 auto-ubiquitin ligase activity, which can promote ubiquitination of wild-type p53 and mutant p53 R273H, and also can form a protein-protein interaction with p53 proteins.
    Conclusion: This information strongly positions MDM2-C as a protein with biochemical activities that may explain the varied outcomes observed in patients with high-level expression of MDM2-C in the presence of wild-type p53 versus mutant p53.
    Language English
    Publishing date 2020-08-24
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2508013-1
    ISSN 1179-1322
    ISSN 1179-1322
    DOI 10.2147/CMAR.S260943
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: Targeting Triple Negative Breast Cancer with a Nucleus-Directed p53 Tetramerization Domain Peptide.

    Xiao, Gu / Annor, George K / Fung, Kimberly / Keinänen, Outi / Zeglis, Brian M / Bargonetti, Jill

    Molecular pharmaceutics

    2020  Volume 18, Issue 1, Page(s) 338–346

    Abstract: Triple negative breast cancer (TNBC) has no targeted detection or treatment method. Mutant p53 (mtp53) is overexpressed in >80% of TNBCs, and the stability of mtp53 compared to the instability of wild-type p53 (wtp53) in normal cells makes mtp53 a ... ...

    Abstract Triple negative breast cancer (TNBC) has no targeted detection or treatment method. Mutant p53 (mtp53) is overexpressed in >80% of TNBCs, and the stability of mtp53 compared to the instability of wild-type p53 (wtp53) in normal cells makes mtp53 a promising TNBC target for diagnostic and theranostic imaging. We generated Cy5p53Tet, a novel nucleus-penetrating mtp53-oligomerization-domain peptide (mtp53ODP) to the tetramerization domain (TD) of mtp53. This mtp53ODP contains the p53 TD sequence conjugated to a Cy5 fluorophore for near-infrared fluorescence imaging (NIRF). In vitro co-immunoprecipitation and glutaraldehyde cross-linking showed a direct interaction between mtp53 and Cy5p53Tet. Confocal microscopy and flow cytometry demonstrated higher uptake of Cy5p53Tet in the nuclei of TNBC MDA-MB-468 cells with mtp53 R273H than in ER-positive MCF7 cells with wtp53. Furthermore, depletion of mtp53 R273H caused a decrease in the uptake of Cy5p53Tet in nuclei. In vivo analysis of the peptide in mice bearing MDA-MB-468 xenografts showed that Cy5p53Tet could be detected in tumor tissue 12 min after injection. In these in vivo experiments, significantly higher uptake of Cy5p53Tet was observed in mtp53-expressing MDA-MB-468 xenografts compared with the wtp53-expressing MCF7 tumors. Cy5p53Tet has clinical potential as an intraoperative imaging agent for fluorescence-guided surgery, and the mtp53ODP scaffold shows promise for modification in the future to enable the delivery of a wide variety of payloads including radionuclides and toxins to mtp53-expressing TNBC tumors.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Nucleus/drug effects ; Cell Proliferation/drug effects ; Female ; Humans ; MCF-7 Cells ; Mice ; Mice, Nude ; Mutation/drug effects ; Peptides/pharmacology ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/metabolism ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Antineoplastic Agents ; Peptides ; TP53 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2020-12-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2138405-8
    ISSN 1543-8392 ; 1543-8384
    ISSN (online) 1543-8392
    ISSN 1543-8384
    DOI 10.1021/acs.molpharmaceut.0c00978
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6250: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article: Oligomerization of Mutant p53 R273H is not Required for Gain-of-Function Chromatin Associated Activities.

    Annor, George K / Elshabassy, Nour / Lundine, Devon / Conde, Don-Gerard / Xiao, Gu / Ellison, Viola / Bargonetti, Jill

    Frontiers in cell and developmental biology

    2021  Volume 9, Page(s) 772315

    Abstract: ... ...

    Abstract The
    Language English
    Publishing date 2021-11-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2021.772315
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: Frame-shift mediated reduction of gain-of-function p53 R273H and deletion of the R273H C-terminus in breast cancer cells result in replication-stress sensitivity.

    Ellison, Viola / Annor, George K / Freedman, Clara / Xiao, Gu / Lundine, Devon / Freulich, Elzbieta / Prives, Carol / Bargonetti, Jill

    Oncotarget

    2021  Volume 12, Issue 12, Page(s) 1128–1146

    Abstract: We recently documented that gain-of-function (GOF) mutant p53 (mtp53) R273H in triple negative breast cancer (TNBC) cells interacts with replicating DNA and PARP1. The missense R273H GOF mtp53 has a mutated central DNA binding domain that renders it ... ...

    Abstract We recently documented that gain-of-function (GOF) mutant p53 (mtp53) R273H in triple negative breast cancer (TNBC) cells interacts with replicating DNA and PARP1. The missense R273H GOF mtp53 has a mutated central DNA binding domain that renders it unable to bind specifically to DNA, but maintains the capacity to interact tightly with chromatin. Both the C-terminal domain (CTD) and oligomerization domain (OD) of GOF mtp53 proteins are intact and it is unclear whether these regions of mtp53 are responsible for chromatin-based DNA replication activities. We generated MDA-MB-468 cells with CRISPR-Cas9 edited versions of the CTD and OD regions of mtp53 R273H. These included a frame-shift mtp53 R273H
    Language English
    Publishing date 2021-06-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.27975
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top