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Regulation of p53 level by UBE4B in breast cancer.

Zhang Y, Lv Y, Zhang Y, Gao H - PLoS ONE (2014)

Bottom Line: The stability of p53 is primarily determined by the RING domain E3 ubiquitin ligase Hdm2, which targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation.UBE4B has been shown to physically interact with p53 and Hdm2 and to negatively regulate p53 stability and function.However, no one has determined whether UBE4B promotes p53 degradation in breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, QiLu Hospital, Jinan, China.

ABSTRACT
p53 is possibly the most important mammalian tumor suppressor and it is mutated or lost in more than half of all human cancers. The stability of p53 is primarily determined by the RING domain E3 ubiquitin ligase Hdm2, which targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. UBE4B has been shown to physically interact with p53 and Hdm2 and to negatively regulate p53 stability and function. However, no one has determined whether UBE4B promotes p53 degradation in breast cancer. In this study, UBE4B promoted the degradation and ubiquitination of p53 to inhibit the apoptosis of cancer cells and promote tumorigenesis. Our results indicate that UBE4B regulates p53 in breast cancer and could be a viable target for developing new therapeutic strategies for breast cancer treatment.

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Related in: MedlinePlus

Interactions of UBE4B with Hdm2 and p53 in vivo.(a) Western blot analysis using UBE4B-specific and p53-specific antibodies after p53 coimmunoprecipitation of from MCF-7 cells and lysates using UBE4B-specific or IgG-specific antibodies. (b) Western blot analysis using anti-UBE4B or anti-p53 antibodies after UBE4B coimmunoprecipitation from MCF-7 cells and lysates using anti-p53 or anti-IgG antibodies. (c) Western blot analysis using UBE4B-specific or Hdm2-specific antibodies after Hdm2 coimmunoprecipitation from MCF-7 cells and lysates using UBE4B-specific or IgG-specific antibodies. (d) Western blot using anti-UBE4B or anti-Hdm2 antibodies after UBE4B coimmunoprecipitation from MCF-7 cells and lysates using anti-Hdm2 or anti-IgG antibodies.
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pone-0090154-g002: Interactions of UBE4B with Hdm2 and p53 in vivo.(a) Western blot analysis using UBE4B-specific and p53-specific antibodies after p53 coimmunoprecipitation of from MCF-7 cells and lysates using UBE4B-specific or IgG-specific antibodies. (b) Western blot analysis using anti-UBE4B or anti-p53 antibodies after UBE4B coimmunoprecipitation from MCF-7 cells and lysates using anti-p53 or anti-IgG antibodies. (c) Western blot analysis using UBE4B-specific or Hdm2-specific antibodies after Hdm2 coimmunoprecipitation from MCF-7 cells and lysates using UBE4B-specific or IgG-specific antibodies. (d) Western blot using anti-UBE4B or anti-Hdm2 antibodies after UBE4B coimmunoprecipitation from MCF-7 cells and lysates using anti-Hdm2 or anti-IgG antibodies.

Mentions: The interaction of UBE4B with Hdm2 and with p53 was tested in MCF7 cells. Immunoprecipitation was performed on the cultured MCF7 cells using anti-UBE4B antibodies. The physiologic interaction between UBE4B and p53 was evaluated using western blot analysis with the respective antibodies (Fig. 2a). Immunoprecipitation in MCF7 cells was conducted using the anti-p53 antibody (Fig. 2b). The results showed that UBE4B interacts with p53. Similar experiments were conducted to determine whether UBE4B interacts with Hdm2 (Figs. 2c and 2d). The results validated the hypothesis that UBE4B interacts with Hdm2. The combined results proved that UBE4B interacts with both p53 and Hdm2.


Regulation of p53 level by UBE4B in breast cancer.

Zhang Y, Lv Y, Zhang Y, Gao H - PLoS ONE (2014)

Interactions of UBE4B with Hdm2 and p53 in vivo.(a) Western blot analysis using UBE4B-specific and p53-specific antibodies after p53 coimmunoprecipitation of from MCF-7 cells and lysates using UBE4B-specific or IgG-specific antibodies. (b) Western blot analysis using anti-UBE4B or anti-p53 antibodies after UBE4B coimmunoprecipitation from MCF-7 cells and lysates using anti-p53 or anti-IgG antibodies. (c) Western blot analysis using UBE4B-specific or Hdm2-specific antibodies after Hdm2 coimmunoprecipitation from MCF-7 cells and lysates using UBE4B-specific or IgG-specific antibodies. (d) Western blot using anti-UBE4B or anti-Hdm2 antibodies after UBE4B coimmunoprecipitation from MCF-7 cells and lysates using anti-Hdm2 or anti-IgG antibodies.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3936002&req=5

pone-0090154-g002: Interactions of UBE4B with Hdm2 and p53 in vivo.(a) Western blot analysis using UBE4B-specific and p53-specific antibodies after p53 coimmunoprecipitation of from MCF-7 cells and lysates using UBE4B-specific or IgG-specific antibodies. (b) Western blot analysis using anti-UBE4B or anti-p53 antibodies after UBE4B coimmunoprecipitation from MCF-7 cells and lysates using anti-p53 or anti-IgG antibodies. (c) Western blot analysis using UBE4B-specific or Hdm2-specific antibodies after Hdm2 coimmunoprecipitation from MCF-7 cells and lysates using UBE4B-specific or IgG-specific antibodies. (d) Western blot using anti-UBE4B or anti-Hdm2 antibodies after UBE4B coimmunoprecipitation from MCF-7 cells and lysates using anti-Hdm2 or anti-IgG antibodies.
Mentions: The interaction of UBE4B with Hdm2 and with p53 was tested in MCF7 cells. Immunoprecipitation was performed on the cultured MCF7 cells using anti-UBE4B antibodies. The physiologic interaction between UBE4B and p53 was evaluated using western blot analysis with the respective antibodies (Fig. 2a). Immunoprecipitation in MCF7 cells was conducted using the anti-p53 antibody (Fig. 2b). The results showed that UBE4B interacts with p53. Similar experiments were conducted to determine whether UBE4B interacts with Hdm2 (Figs. 2c and 2d). The results validated the hypothesis that UBE4B interacts with Hdm2. The combined results proved that UBE4B interacts with both p53 and Hdm2.

Bottom Line: The stability of p53 is primarily determined by the RING domain E3 ubiquitin ligase Hdm2, which targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation.UBE4B has been shown to physically interact with p53 and Hdm2 and to negatively regulate p53 stability and function.However, no one has determined whether UBE4B promotes p53 degradation in breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, QiLu Hospital, Jinan, China.

ABSTRACT
p53 is possibly the most important mammalian tumor suppressor and it is mutated or lost in more than half of all human cancers. The stability of p53 is primarily determined by the RING domain E3 ubiquitin ligase Hdm2, which targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. UBE4B has been shown to physically interact with p53 and Hdm2 and to negatively regulate p53 stability and function. However, no one has determined whether UBE4B promotes p53 degradation in breast cancer. In this study, UBE4B promoted the degradation and ubiquitination of p53 to inhibit the apoptosis of cancer cells and promote tumorigenesis. Our results indicate that UBE4B regulates p53 in breast cancer and could be a viable target for developing new therapeutic strategies for breast cancer treatment.

Show MeSH
Related in: MedlinePlus