Control of p53 multimerization by Ubc13 is JNK-regulated.
The p53 tumor suppressor protein is a key regulator of cellular proliferation and survival whose function is tightly regulated at the levels of transcription and protein stability. Here, we unveil the fine control of p53 on translationally active polysomes. We have previously reported that Ubc13, an E2 ubiquitin-conjugating enzyme, directly regulates p53 localization and transcriptional activity. We now demonstrate that the association of p53 and Ubc13 on polysomes requires ongoing translation and results in p53 ubiquitination that interferes with its tetramerization. JNK phosphorylation of p53 at Threonine 81 occurring on polysomes is required for the dissociation of Ubc13 from p53, leading to p53 multimerization and transcriptional activation. Inhibition of JNK activity or expression of a nonphosphorylatable mutant of p53 maintains an Ubc13-p53 complex that inhibits p53 multimerization. Our findings reveal a layer in the regulation of p53 multimerization that requires the concerted action of JNK and Ubc13 on polysome-bound p53.
Topisirovic
Ivan
I
Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Quebec, H3T 1J4, Canada.
Gutierrez
Gustavo J
GJ
Chen
Meifan
M
Appella
Ettore
E
Borden
Katherine L B
KL
Ronai
Ze'ev A
ZA
D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D020935:MAP Kinase Signaling System; D011132:Polyribosomes / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry / Q000502:physiology*
D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C471607:UBE2N protein, human; D044763:Ubiquitin-Conjugating Enzymes; D048031:JNK Mitogen-Activated Protein Kinases