PML is required for homeodomain-interacting protein kinase 2 (HIPK2)-mediated p53 phosphorylation and cell cycle arrest but is dispensable for the formation of HIPK domains.

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Citation

Moller A, Sirma H, Hofmann TG, Rueffer S, Klimczak E, Droge W, Will H, Schmitz ML

PML is required for homeodomain-interacting protein kinase 2 (HIPK2)-mediated p53 phosphorylation and cell cycle arrest but is dispensable for the formation of HIPK domains.

Cancer Res. 2003 Aug 1;63(15):4310-4.

PubMed ID
12907596 [ View in PubMed
]
Abstract

Here we demonstrate that endogenous human homeodomain-interacting protein kinase (HIPK) 2 and the highly homologous kinase HIPK3 are found in a novel subnuclear domain, the HIPK domains. These are distinct from other subnuclear structures such as Cajal bodies and nucleoli and show only a partial colocalization with promyelocytic leukemia (PML) nuclear bodies (PML-NBs). A kinase inactive HIPK2 point mutant is localized in the nucleoplasm. The occurrence of HIPK domains in PML-/- fibroblasts reveals their independence from the PML protein. HIPK2 can be almost completely recruited to PML-NBs by the PML isoform PML IV, but not by PML-III. PML IV-mediated recruitment of HIPK2 does not rely on its kinase function and also occurs in PML-/- fibroblasts, showing that this PML isoform is sufficient for recruitment of HIPK2. Whereas the architecture of HIPK domains is PML independent, HIPK2-mediated enhancement of p53-dependent transcription, p53 serine 46 phosphorylation and the antiproliferative function of HIPK2 strictly rely on the presence of PML.

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Polypeptides
NameUniProt ID
Homeodomain-interacting protein kinase 2Q9H2X6Details