Control of nuclear HIPK2 localization and function by a SUMO interaction motif

Laureano de la Vega, Katrin Fröbius, Rita Moreno, Marco A. Calzado, Hui Geng, M. Lienhard Schmitz

    Research output: Contribution to journalArticlepeer-review

    33 Citations (Scopus)

    Abstract

    The serine/threonine kinase HIPK2 regulates gene expression programs controlling differentiation and cell death. HIPK2 localizes in subnuclear speckles, but the structural components allowing this localization are not understood. A point mutation analysis allowed mapping two nuclear localization signals and a SUMO interaction motif (SIM) that also occurs in HIPK1 and HIPK3. The SIM binds all three major isoforms of SUMO (SUMO-1-3), while only SUMO-1 is capable of covalent conjugation to HIPK2. Deletion or mutation of the SIM prevented SUMO binding and precluded localization of HIPK2 in nuclear speckles, thus causing localization of HIPK2 to the entire cell. Functional inactivation of the SIM prohibited recruitment of HIPK2 to PML nuclear bodies and disrupted colocalization with other proteins such as the polycomb protein Pc2 in nuclear speckles. Interaction of HIPK2 with Pc2 or PML in intact cells was largely dependent on a functional SIM in HIPK2, highlighting the relevance of SUMO/SIM interactions as a molecular glue that serves to enhance protein/protein interaction networks. HIPK2 mutants with an inactive SIM showed changed activities, thus revealing that non-covalent binding of SUMO to the kinase is important for the regulation of its function.
    Original languageEnglish
    Pages (from-to)283-297
    Number of pages15
    JournalBiochimica et Biophysica Acta (BBA) - Molecular Cell Research
    Volume1813
    Issue number2
    DOIs
    Publication statusPublished - Feb 2011

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