RNF38 encodes a nuclear ubiquitin protein ligase that modifies p53

•RNF38 is shown to be a nuclear protein with a bipartite nuclear localization signal.•RNF38 protein is purified and shown to have ubiquitin protein ligase (E3) activity.•We show that RNF38 binds p53 and can ubiquitinate p53 in vitro.•Overexpression of RNF38 increases p53 ubiquitination in HEK293T ce...

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Bibliographic Details
Published in:	Biochemical and biophysical research communications 2013-11, Vol.440 (4), p.473-478
Main Authors:	Sheren, Jamie E., Kassenbrock, C. Kenneth
Format:	Article
Language:	eng
Subjects:	60 APPLIED LIFE SCIENCES Amino Acid Sequence Carrier Proteins - genetics Carrier Proteins - metabolism Cell Nucleus - enzymology FINGERS GENES HEK293 Cells Humans IN VITRO IN VIVO Intranuclear Inclusion Bodies - enzymology LIGASES Molecular Sequence Data Nuclear Localization Signals - genetics Nuclear Localization Signals - metabolism Nuclear Proteins - metabolism p53 PML nuclear bodies Promyelocytic Leukemia Protein RNF38 Transcription Factors - metabolism Tumor Suppressor Proteins - metabolism Ubiquitin protein ligase Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - metabolism Ubiquitination Zinc Fingers
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Summary:	•RNF38 is shown to be a nuclear protein with a bipartite nuclear localization signal.•RNF38 protein is purified and shown to have ubiquitin protein ligase (E3) activity.•We show that RNF38 binds p53 and can ubiquitinate p53 in vitro.•Overexpression of RNF38 increases p53 ubiquitination in HEK293T cells.•Overexpression of RNF38 in HEK293T cells alters p53 localization. The RNF38 gene encodes a RING finger protein of unknown function. Here we demonstrate that RNF38 is a functional ubiquitin protein ligase (E3). We show that RNF38 isoform 1 is localized to the nucleus by a bipartite nuclear localization sequence (NLS). We confirm that RNF38 is a binding partner of p53 and demonstrate that RNF38 can ubiquitinate p53 in vitro and in vivo. Finally, we show that overexpression of RNF38 in HEK293T cells results in relocalization of p53 to discrete foci associated with PML nuclear bodies. These results suggest RNF38 is an E3 ubiquitin ligase that may play a role in regulating p53.
ISSN:	0006-291X 1090-2104