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dc.contributor.authorBultsma, Yvette
dc.contributor.authorKeune, Willem-Jan
dc.contributor.authorDivecha, Nullin
dc.date.accessioned2010-09-18T08:59:27Z
dc.date.available2010-09-18T08:59:27Z
dc.date.issued2010-08-13
dc.identifier.citationPIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha. 2010, 430 (2):223-35 Biochem Jen
dc.identifier.issn0264-6021
dc.identifier.pmid20583997
dc.identifier.doi10.1042/BJ20100341
dc.identifier.urihttp://hdl.handle.net/10541/111378
dc.description.abstractThe beta-isoform of PIP4K (PtdIns5P-4-kinase) regulates the levels of nuclear PtdIns5P, which in turn modulates the acetylation of the tumour suppressor p53. The crystal structure of PIP4Kbeta demonstrated that it can form a homodimer with the two subunits arranged in opposite orientations. Using MS, isoform-specific antibodies against PIP4Ks, RNAi (RNA interference) suppression and overexpression studies, we show that PIP4Kbeta interacts in vitro and in vivo with the PIP4Kalpha isoform. As the two isoforms phosphorylate the same substrate to generate the same product, the interaction could be considered to be functionally redundant. However, contrary to expectation, we find that PIP4Kbeta has 2000-fold less activity towards PtdIns5P compared with PIP4Kalpha, and that the majority of PIP4K activity associated with PIP4Kbeta comes from its interaction with PIP4Kalpha. Furthermore, PIP4Kbeta can modulate the nuclear localization of PIP4Kalpha, and PIP4Kalpha has a role in regulating PIP4Kbeta functions. The results of the present study suggest a rationale for the functional interaction between PIP4Kalpha and PIP4Kbeta and provide insight into how the relative levels of the two enzymes may be important in their physiological and pathological roles.
dc.language.isoenen
dc.subjectTumour Cell Lineen
dc.subject.meshCell Line, Tumor
dc.subject.meshCell Nucleus
dc.subject.meshHumans
dc.subject.meshPhosphotransferases (Alcohol Group Acceptor)
dc.subject.meshProtein Binding
dc.subject.meshProtein Isoforms
dc.subject.meshProtein Transport
dc.titlePIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha.en
dc.typeArticleen
dc.identifier.eissn1470-8728
dc.contributor.departmentCRUK Inositide Laboratory, the Paterson Institute for Cancer Research, Wilmslow Road, Manchester, UK.en
dc.identifier.journalThe Biochemical Journalen
html.description.abstractThe beta-isoform of PIP4K (PtdIns5P-4-kinase) regulates the levels of nuclear PtdIns5P, which in turn modulates the acetylation of the tumour suppressor p53. The crystal structure of PIP4Kbeta demonstrated that it can form a homodimer with the two subunits arranged in opposite orientations. Using MS, isoform-specific antibodies against PIP4Ks, RNAi (RNA interference) suppression and overexpression studies, we show that PIP4Kbeta interacts in vitro and in vivo with the PIP4Kalpha isoform. As the two isoforms phosphorylate the same substrate to generate the same product, the interaction could be considered to be functionally redundant. However, contrary to expectation, we find that PIP4Kbeta has 2000-fold less activity towards PtdIns5P compared with PIP4Kalpha, and that the majority of PIP4K activity associated with PIP4Kbeta comes from its interaction with PIP4Kalpha. Furthermore, PIP4Kbeta can modulate the nuclear localization of PIP4Kalpha, and PIP4Kalpha has a role in regulating PIP4Kbeta functions. The results of the present study suggest a rationale for the functional interaction between PIP4Kalpha and PIP4Kbeta and provide insight into how the relative levels of the two enzymes may be important in their physiological and pathological roles.


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