LNX1 contributes to tumor growth by down-regulating p53 stability

Rackhyun Park, Hyunju Kim, Minsu Jang, Daum Jo, Yea In Park, Sim Namkoong, Jin I. Lee, Ik Soon Jang, Junsoo Park

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5 Citations (Scopus)


The well-known tumor suppressor p53 inhibits the formation of various cancers by inducing cell cycle arrest and apoptosis. Although p53 mutations are commonly found in many cancers, p53 is functionally inactivated in tumor cells that retain wild-type p53. Here, we show that the ligand of numb protein X1 (LNX1) inhibited p53-dependent transcription by decreasing the half-life of p53. We generated LNX1 knockout (KO) cells in p53 wild-type cancer cells (A549, HCT116, and MCF7) using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 gene-editing system. LNX1 KO activated p53-dependent transcription by increasing the stability of p53. Moreover, lentivirus-mediated overexpression of LNX1 decreased p53 protein levels and inhibited p53-dependent transcription. LNX1 interacted with p53 and mouse double minute 2 (MDM2) and increased the ubiquitination of p53 in an MDM2-dependent manner. Finally, we demonstrated that LNX1 was required for efficient tumor growth both in cell culture and in a mouse tumor xenograft model. These results collectively indicated that LNX1 contributed to tumor growth by inhibiting p53-dependent signaling in p53 wild-type cancer cells.—Park, R., Kim, H., Jang M., Jo, D., Park, Y.-I., Namkoong S., Lee, J. I., Jang I.-S., Park, J. LNX1contributes to tumor growth by down-regulating p53 stability. FASEB J. 33, 13216–13227 (2019). www.fasebj.org.

Original languageEnglish
Pages (from-to)13216-13227
Number of pages12
JournalFASEB Journal
Issue number12
Publication statusPublished - 2019 Dec

Bibliographical note

Funding Information:
This study was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (2016R1A2B4009665 and 2019R1A2C1006511). The authors declare no conflicts of interest.

Publisher Copyright:

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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