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The interaction between p53 and Mdm2 is independent of MEG3–p53 association
Author(s) -
Bauer Nicholas C.,
Yang Anli,
Wang Xin,
Zhou Yunli,
Klibanski Anne,
Soberman Roy J.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09899
Subject(s) - mdm2 , meg3 , context (archaeology) , suppressor , ubiquitin ligase , computational biology , in vivo , physics , rna , chemistry , biophysics , biology , ubiquitin , biochemistry , apoptosis , long non coding rna , genetics , gene , paleontology
The ability of the long noncoding RNA MEG3 to suppress cell proliferation led to its recognition as a tumor suppressor. MEG3 has previously been shown to bind to p53 in vitro, which led us to hypothesize that MEG3 functions by disrupting the interaction of p53 and its E3 ubiquitin ligase Mdm2. To test this hypothesis in vivo, we built a cross‐nearest neighbor/Monte Carlo analytical method based on two color direct stochastic optical reconstruction microscopy (dSTORM), a single‐molecule localization microscopy (SMLM) technique. Our data support the interaction of MEG3 and p53. Surprisingly, this association had no effect on the binding of p53 and Mdm2, distinct from the most commonly proposed model for the mechanism of MEG3 action. Additionally, our mathematical approach to analyzing SMLM data has general applicability to assessing molecular interactions in a native cellular context. Support or Funding Information RJS: NIH R01CA193520, NIH R01DK062472, NIH S10RR027931; NCB: NIH T32DK007540; AK and YZ: NIH R01CA193520; and The Jarislowsky Foundation