<big dropzone="bkWTds3t"><noframes id="z1c4BQM"> VSports在线直播 - Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil VSports app下载. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

. 2020 Apr 16;12(4):985.
doi: 10.3390/cancers12040985.

"V体育官网入口" p53 and FBXW7: Sometimes Two Guardians Are Worse than One

María Galindo-Moreno  1 , Servando Giráldez  1 , M Cristina Limón-Mortés  1 , Alejandro Belmonte-Fernández  1 , Carmen Sáez  2   3 , Miguel Á Japón  2   3 , Maria Tortolero  1 , Francisco Romero  1
Affiliations

p53 and FBXW7: Sometimes Two Guardians Are Worse than One

María Galindo-Moreno et al. Cancers (Basel). .

Abstract

Too much of a good thing can become a bad thing. An example is FBXW7, a well-known tumor suppressor that may also contribute to tumorigenesis VSports手机版. Here, we reflect on the results of three laboratories describing the role of FBXW7 in the degradation of p53 and the possible implications of this finding in tumor cell development. We also speculate about the function of FBXW7 as a key player in the cell fate after DNA damage and how this could be exploited in the treatment of cancer disease. .

Keywords: FBXW7; cancer; p53; proliferation; tumor suppressor; ubiquitylation V体育安卓版. .

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results V体育ios版.

Figures (V体育2025版)

Figure 1
Figure 1
A simplified model for the role of the SCF(FBXW7) ubiquitin ligase as guardian of the correct cellular response to DNA damage. Under unstressed conditions, PLK1 phosphorylates various proteins that promote DNA replication. Upon DNA damage, SCF(FBXW7) targets PLK1 for proteasomal degradation, arresting cell cycle in S-phase. On the other hand, mainly MDM2, but also other ubiquitin ligases, maintain low levels of p53 under normal growth conditions. After DNA damage, p53 accumulates and arrests the cell cycle to allow damage to be repaired. After that, p53 levels decrease again due to SCF(FBXW7) and others, to recover cell cycle progression.
See this image and copyright information in PMC

References

    1. Welcker M., Orian A., Jin J., Grim J.E., Harper J.W., Eisenman R.B., Clurman B.E. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc. Natl. Acad. Sci. USA. 2004;101:9085–9090. doi: 10.1073/pnas.0402770101. - DOI - PMC - PubMed
    1. Koepp D.M., Schaefer L.K., Ye X., Keyomarsi K., Chu C., Harper J.W., Elledge S.J. Phosphorylation- dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science. 2001;294:173–177. doi: 10.1126/science.1065203. - DOI - PubMed
    1. Inuzuka H., Shaik S., Onoyama I., Gao D., Tseng A., Maser R.S., Zhai B., Wan L., Gutierrez A., Lau A.W., et al. SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature. 2011;471:104–109. doi: 10.1038/nature09732. - DOI - PMC - PubMed
    1. Mao J.H., Kim I.J., Wu D., Climent J., Kang H.C., DelRosario R., Balmain A. FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression. Science. 2008;321:1499–1502. doi: 10.1126/science.1162981. - DOI - PMC - PubMed
    1. Wei W., Jin J., Schlisio S., Harper J.W., Kaelin W.G., Jr. The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell. 2005;8:25–33. doi: 10.1016/j.ccr.2005.06.005. - DOI (V体育2025版) - PubMed