SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells

Sung Wook Park, Xinli Hu, Pawan Gupta, Ya Ping Lin, Sung Gil Ha, Li-Na Wei

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


The Tr2 orphan nuclear receptor can be SUMOylated, resulting in the replacement of coregulators recruited to the regulatory region of its endogenous target gene, Oct4. UnSUMOylated Tr2 activates Oct4, enhancing embryonal carcinoma-cell proliferation, and is localized to the promyelocytic leukemia (Pml) nuclear bodies. When its abundance is elevated, Tr2 is SUMOylated at Lys238 and seems to be released from the nuclear bodies to act as a repressor. SUMOylation of Tr2 induces an exchange of its coregulators: corepressor Rip140 replaces coactivator Pcaf, which switches Tr2 from an activator to a repressor. This involves dynamic partitioning of Tr2 into Pml-containing and Pml-free pools. These results support a model where SUMOylation-dependent partitioning and differential coregulator recruitment contribute to the maintenance of a homeostatic supply of activating, as opposed to repressive, Tr2, thus fine-tuning Oct4 expression and regulating stem-cell proliferation.

Original languageEnglish (US)
Pages (from-to)68-75
Number of pages8
JournalNature Structural and Molecular Biology
Issue number1
StatePublished - Jan 2007

Bibliographical note

Funding Information:
This work was supported by US National Institutes of Health grants DK54733, DK60521, K02 DA13926 and DA11190 to L.-N.W. We also thank C.H. Lee and C. Chainpaisal for yeast screening and N.P. Tsai, F.C. Walosin and S.D. Persaud for technical support.


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