Journal
FEBS JOURNAL
Volume 289, Issue 3, Pages 748-765Publisher
WILEY
DOI: 10.1111/febs.16187
Keywords
AP-1; c-Jun; Fra2; nucleolar localization sequence; nucleolus
Categories
Funding
- NSERC [RGPIN-2018-05896]
- CIHR [PJT-159644]
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This study reveals that the proto-oncogene c-Jun can be targeted to the nucleolus, and its basic domain contains a unique motif that determines nucleolar localization. While partners such as Fra2 do not co-localize with c-Jun in the nucleolus. A point mutation can result in loss of nucleolar targeting for c-Jun, while its nuclear localization remains intact.
Nucleoli are well defined for their function in ribosome biogenesis, but only a small fraction of the nucleolar proteome has been characterized. Here, we report that the proto-oncogene, c-Jun, is targeted to the nucleolus. Using live cell imaging in myogenic cells, we document that the c-Jun basic domain contains a unique, evolutionarily conserved motif that determines nucleolar targeting. Fos family Jun dimer partners, such as Fra2, while nuclear, do not co-localize with c-Jun in the nucleolus. A point mutation in c-Jun that mimics Fra2 (M260E) in its Nucleolar Localization sequence (NoLS) results in loss of c-Jun nucleolar targeting while still preserving nuclear localization. Fra2 can sequester c-Jun in the nucleoplasm, indicating that the stoichiometric ratio of heterodimeric partners regulates c-Jun nucleolar targeting. Finally, nucleolar localization of c-Jun modulates nucleolar architecture and ribosomal RNA accumulation. These studies highlight a novel role for Jun family proteins in the nucleolus, having potential implications for a diverse array of AP-1-regulated cellular processes.
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