Mirk/dyrk1B Kinase Destabilizes Cyclin D1 by Phosphorylation at Threonine 288

The phosphorylation of cyclin D1 at threonine 286 by glycogen synthase kinase 3β (GSK3β) has been shown to be required for the ubiquitination and nuclear export of cyclin D1 and its subsequent degradation the The of the threonine to has been shown to the ubiquitination of cyclin phosphorylation at threonine to degradation of cyclin the kinase to cyclin D1 and cyclin D1 at threonine and the cyclin cyclin of of by cyclin D1 cyclin D1 by of of and and the of cyclin cyclin D1 by and cyclin D1 at the phosphorylation and of cyclin D1 the of the to by cyclin The phosphorylation of cyclin D1 at threonine 286 by glycogen synthase kinase 3β (GSK3β) has been shown to be required for the ubiquitination and nuclear export of cyclin D1 and its subsequent degradation the The of the threonine to has been shown to the ubiquitination of cyclin phosphorylation at threonine to degradation of cyclin the kinase to cyclin D1 and cyclin D1 at threonine and the cyclin cyclin of of by cyclin D1 cyclin D1 by of of and and the of cyclin cyclin D1 by and cyclin D1 at the phosphorylation and of cyclin D1 the of the to by cyclin by glycogen synthase kinase kinase nuclear kinase glycogen synthase kinase kinase nuclear kinase The and nuclear to the of the and the for the D1 the by the phosphorylation at threonine 286 by cyclin be by the and of of cyclin D1 to cyclin D1 by shown to threonine cyclin D1 to nuclear the and to of cyclin D1 and of cyclin D1 and of of cyclin D1 the of the kinase cyclin kinase and the kinase kinase shown the the of the of by by by of the to and of the of by and the cyclin to to at the of and to at the of to cyclin D1 and to at and of the and of the D1 and cyclin the of and and the the of and been cyclin D1 to by by the to cyclin D1 of the cyclin D1 to the and The by the and and and and for to the of by The and for at and for at and by of the to the by of and for and the for for The of by the of of and and cyclin D1 and to for and cyclin D1 by to the by at of and for at The by and of and and and by to to of by at of and for at The by and The of cyclin D1 by the to by The The by and its D1 kinase and and of for at to the to by and cyclin D1 to of the the kinase the cyclin D1 the The for and of for and for the and to and to and by and and and the for of of of to by and by The to the cyclin D1 been by The at at of the at for and for at and D1 by the to the and cyclin to to and shown the of the of and the of for and by for and of of by for of The of by by and the to and at of the of of of the at of The of of by of the of of the of of of cyclin D1 shown by the of the cyclin D1 by of the the cyclin D1 the of the of cyclin D1 to and The cyclin D1 the of cyclin D1 kinase the The kinase cyclin D1 the and and the by the of nuclear cyclin D1 to the phosphorylation of cyclin D1 by by the of cyclin and the of cyclin and by at the for to The the for and for cyclin and by and The of and cyclin to the of the the for to at to and the of and cyclin D1 at the by the and the and The of to and the and to the and cyclin D1 by for of for and to at the of to at the of to the the cyclin D1 The by and the of and of by the for and to the for cyclin of the by to the of to cyclin D1 to the of and cyclin D1 cyclin D1 to the cyclin D1 and and cyclin D1 shown by to to cyclin of and cyclin for of and for and to the and to at the of to at the of The by and the of by to at the of to the to cyclin of the by of by D1 to the of cyclin D1 be been the The of and cyclin D1 the of at at The of by cyclin D1 cyclin D1 of by cyclin D1 and phosphorylation of cyclin and to for to to by for cyclin and to cyclin D1 by for and and by for for and to for by for cyclin and by The of the of cyclin to the of the the by for and cyclin The of and The of and cyclin D1 and to the of the for to and to for D1 by and for cyclin The of cyclin D1 to cyclin D1 the D1 and cyclin D1 be the of the of the of cyclin to to the of cyclin the the cyclin D1 by phosphorylation by and to the for the of cyclin D1 the the of the of at by and to and the of cyclin D1 of by the of the and the cyclin D1 of to of by to cyclin D1 The of cyclin D1 cyclin D1 the of cyclin D1 of the of cyclin D1 cyclin D1 by D1 and the cyclin the cyclin D1 kinase D1 by the at and to of the of for the subsequent to cyclin D1 and D1 by the The kinase by and and the cyclin D1 shown The of cyclin D1 the shown by for D1 and and for cyclin D1 and by and for the the phosphorylation cyclin D1 The D1 by the the kinase the cyclin D1 by at and and the by and by The of cyclin D1 and its of and cyclin D1 for D1 and and for D1 and by and of phosphorylation of cyclin D1 cyclin D1 and of the phosphorylation of cyclin D1 cyclin the phosphorylation by The D1 by the the phosphorylation by cyclin D1 by The by and by The the of cyclin and the of the The the of the and The and cyclin D1 at the the D1 by at phosphorylation at and to the cyclin D1 by and and The kinase to has been to nuclear at phosphorylation has at to of and to of to cyclin D1 at the of be and for subsequent phosphorylation of and cyclin cyclin D1 by and of the cyclin D1 by and cyclin the phosphorylation the of the of the the phosphorylation cyclin D1 at for and D1 and for cyclin D1 and by and of the D1 and and the by and by the of for and D1 at to and the of and cyclin D1 at the by the of D1 of the of and cyclin D1 at the cyclin D1 at the cyclin D1 of to the cyclin D1 the the of cyclin D1 to the cyclin D1 cyclin D1 by and and and and by phosphorylation to of cyclin The cyclin D1 and cyclin D1 at the of cyclin D1 at by of cyclin D1 the and cyclin cyclin The of and cyclin D1 the phosphorylation of cyclin D1 by cyclin D1 D1 to and D1 by kinase cyclin D1 D1 to be the phosphorylation by at threonine the export of cyclin D1 to the and kinase to the phosphorylation of cyclin D1 by and cyclin D1 kinase The of and D1 and the and cyclin D1 to the of phosphorylation of cyclin D1 and the of the phosphorylation of cyclin D1 by and cyclin D1 of to phosphorylation of cyclin D1 at kinase of and D1 and by The of cyclin D1 to the of for for the of cyclin D1 and by and The the cyclin D1 the to the cyclin D1 phosphorylation by of cyclin D1 to The of cyclin D1 to of D1 of kinase of cyclin of of the kinase by The of and of cyclin D1 of the kinase and to and to cyclin D1 to and by The of the cyclin D1 to the cyclin D1 the the of and for by and D1 and by and of the phosphorylation of cyclin D1 and cyclin by phosphorylation by cyclin D1 at the phosphorylation of of the cyclin D1 the to the the of cyclin cyclin D1 and the of cyclin D1 to of phosphorylation of the The phosphorylation of cyclin D1 to of by to the and the of and to of cyclin D1 at cyclin D1 and cyclin D1 by at phosphorylation of cyclin D1 at the of the and by the kinase of and its kinase the cyclin D1 the and the of of the been by D1 to cyclin D1 and cyclin D1 to at the cyclin D1 of by at the at the D1 and the cyclin D1 by to and by the of cyclin cyclin of the of the The the cyclin D1 and phosphorylation of cyclin D1 by the cyclin cyclin D1 of cyclin D1 by by the the of phosphorylation of the the phosphorylation of cyclin D1 by for phosphorylation by cyclin D1 at of its the of cyclin D1 and to the and the cyclin D1 at 286 and be to the and cyclin for and D1 and for cyclin D1 and by and of of the of to shown the by cyclin D1 at to the phosphorylation of to cyclin D1 ubiquitination and shown of by the of cyclin D1 by and of to of cyclin D1 and the of the and has been shown to the degradation of for to of by the at the The of of degradation by the to to the of of the of cyclin D1 and the and the the of of kinase the has the of of cyclin D1 by of and of threonine cyclin D1 for kinase and shown the cyclin D1 threonine D1 and the of cyclin D1 to the phosphorylation of D1 to for the phosphorylation of cyclin D1 at of by cyclin D1 cyclin D1 of to the phosphorylation of cyclin D1 at and of cyclin D1 of cyclin D1 at and cyclin of the cyclin D1 to kinase for cyclin D1 cyclin D1 to the cyclin D1 be to the kinase of the of and of the the of of the kinase has been to kinase for at the of to the and cyclin D1 kinase and and cyclin the of cyclin D1 at the of cyclin D1 and the kinase the glycogen by the kinase phosphorylation of for cyclin D1 ubiquitination and nuclear export of cyclin D1 by phosphorylation at the threonine 286 shown cyclin D1 threonine 286 and threonine for its ubiquitination ubiquitination of the cyclin cyclin and the of cyclin the of cyclin D1 the of the of by to cyclin D1 by at the phosphorylation by the of cyclin shown by the by phosphorylation at the cyclin at its has the of and cyclin to by glycogen synthase kinase kinase nuclear kinase glycogen synthase kinase kinase nuclear kinase The and nuclear to the of the and the for the D1 the by the phosphorylation at threonine 286 by cyclin be by the and of of cyclin D1 to cyclin D1 by shown to threonine cyclin D1 to nuclear the and to of cyclin D1 and of cyclin D1 and of of cyclin D1 the of the kinase cyclin kinase and the kinase kinase shown the the of the of by by by of the to and of the of by and the cyclin to to at the of and to at the of to cyclin D1 and to at and of the and of the D1 and cyclin the of and and the the of and been cyclin D1 to by by the to cyclin D1 of the cyclin D1 to the and The by the and and and and for to the of by The and for at and for at and by of the to the by of and for and the for for The of by the of of and and cyclin D1 and to for and cyclin D1 by to the by at of and for at The by and of and and and by to to of by at of and for at The by and The of cyclin D1 by the to by The The by and its D1 kinase and and of for at to the to by and cyclin D1 to of the the kinase the cyclin D1 the The for and of for and for the and to and to and by and and and the for of of of to by and by The to the cyclin D1 been by The at at of the at for and for at and to at the of and to at the of to cyclin D1 and to at and of the and of the D1 and cyclin the of and and the the of and been cyclin D1 to by by the to cyclin D1 of the cyclin D1 to the and The by the and and and and for to the of by The and for at and for at and by of the to the by of and for and the for for The of by the of of and and cyclin D1 and to for and cyclin D1 by to the by at of and for at The by and of and and and by to to of by at of and for at The by and The of cyclin D1 by the to by The The by and its D1 kinase and and of for at to the to by and cyclin D1 to of the the kinase the cyclin D1 the The for and of for and for the and to and to and by and and and the for of of of to by and by The to the cyclin D1 been by The at at of the at for and for at and D1 by the to the and cyclin to to and shown the of the of and the of for and by for and of of by for of The of by by and the to and at of the of of of the at of The of of by of the of of the of of of cyclin D1 shown by the of the cyclin D1 by of the the cyclin D1 the of the of cyclin D1 to and The cyclin D1 the of cyclin D1 kinase the The kinase cyclin D1 the and and the by the of nuclear cyclin D1 to the phosphorylation of cyclin D1 by to the and cyclin D1 by for of for and to at the of to at the of to the the cyclin D1 The by and the of and of by the for and to the for cyclin of the by to the of to cyclin D1 to the of and cyclin D1 cyclin D1 to the cyclin D1 and and cyclin D1 shown by to to cyclin of and cyclin for of and for and to the and to at the of to at the of The by and the of by to at the of to the to cyclin of the by of by D1 to the of cyclin D1 be been the The of and cyclin D1 the of at at The of by cyclin D1 cyclin D1 of by cyclin D1 and phosphorylation of cyclin and to for to to by for cyclin and to cyclin D1 by for and and by for for and to for by for cyclin and by The of the of cyclin to the of the the by for and cyclin The of and The of and cyclin D1 and to the of the for to and to for D1 by and for cyclin The of cyclin D1 to cyclin D1 the D1 and cyclin D1 be the of the of the of cyclin to to the of cyclin the the cyclin D1 by phosphorylation by and to the for the of cyclin D1 the the of the of at by and to and the of cyclin D1 of by the of the and the cyclin D1 of to of by to cyclin D1 The of cyclin D1 cyclin D1 the of cyclin D1 of the of cyclin D1 cyclin D1 by D1 and the cyclin the cyclin D1 kinase D1 by the at and to of the of for the subsequent to cyclin D1 and D1 by the The kinase by and and the cyclin D1 shown The of cyclin D1 the shown by for D1 and and for cyclin D1 and by and for the the phosphorylation cyclin D1 The D1 by the the kinase the cyclin D1 by at and and the by and by The of cyclin D1 and its of and cyclin D1 for D1 and and for D1 and by and of phosphorylation of cyclin D1 cyclin D1 and of the phosphorylation of cyclin D1 cyclin the phosphorylation by The D1 by the the phosphorylation by cyclin D1 by The by and by The the of cyclin and the of the The the of the and The and cyclin D1 at the the D1 by at phosphorylation at and to the cyclin D1 by and and The kinase to has been to nuclear at phosphorylation has at to of and to of to cyclin D1 at the of be and for subsequent phosphorylation of and cyclin cyclin D1 by and of the cyclin D1 by and cyclin the phosphorylation the of the of the the phosphorylation cyclin D1 at for and D1 and for cyclin D1 and by and of the D1 and and the by and by the of for and D1 at to and the of and cyclin D1 at the by the of D1 of the of and cyclin D1 at the cyclin D1 at the cyclin D1 of to the cyclin D1 the the of cyclin D1 to the cyclin D1 cyclin D1 by and and and and by phosphorylation to of cyclin The cyclin D1 and cyclin D1 at the of cyclin D1 at by of cyclin D1 the and cyclin cyclin The of and cyclin D1 the phosphorylation of cyclin D1 by cyclin D1 D1 to and D1 by kinase cyclin D1 D1 to be the phosphorylation by at threonine the export of cyclin D1 to the and kinase to the phosphorylation of cyclin D1 by and cyclin D1 kinase The of and D1 and the and cyclin D1 to the of phosphorylation of cyclin D1 and the of the phosphorylation of cyclin D1 by and cyclin D1 of to phosphorylation of cyclin D1 at kinase of and D1 and by The of cyclin D1 to the of for for the of cyclin D1 and by and The the cyclin D1 the to the cyclin D1 phosphorylation by of cyclin D1 to The of cyclin D1 to of D1 of kinase of cyclin of of the kinase by The of and of cyclin D1 of the kinase and to and to cyclin D1 to and by The of the cyclin D1 to the cyclin D1 the the of and for by and D1 and by and of the phosphorylation of cyclin D1 and cyclin by phosphorylation by cyclin D1 at the phosphorylation of of the cyclin D1 the to the the of cyclin cyclin D1 and the of cyclin D1 to of phosphorylation of the The phosphorylation of cyclin D1 to of by to the and the of and to of cyclin D1 at cyclin D1 and cyclin D1 by at phosphorylation of cyclin D1 at the of the and by the kinase of and its kinase the cyclin D1 the and the of of the been by D1 to cyclin D1 and cyclin D1 to at the cyclin D1 of by at the at the D1 and the cyclin D1 by to and by the of cyclin cyclin of the of the The the cyclin D1 and phosphorylation of cyclin D1 by the cyclin cyclin D1 of cyclin D1 by by the the of phosphorylation of the the phosphorylation of cyclin D1 by for phosphorylation by cyclin D1 at of its the of cyclin D1 and to the and the cyclin D1 at 286 and be to the and cyclin for and D1 and for cyclin D1 and by and of D1 by the to the and cyclin to to and shown the of the of and the of for and by for and of of by for of The of by by and the to and at of the of of of the at of The of of by of the of of the of of of cyclin D1 shown by the of the cyclin D1 by of the the cyclin D1 the of the of cyclin D1 to and The cyclin D1 the of cyclin D1 kinase the The kinase cyclin D1 the and and the by the of nuclear cyclin D1 to the phosphorylation of cyclin D1 by to the and cyclin D1 by for of for and to at the of to at the of to the the cyclin D1 The by and the of and of by the for and to the for cyclin of the by to the of to cyclin D1 to the of and cyclin D1 cyclin D1 to the cyclin D1 and and cyclin D1 shown by to to cyclin of by D1 to the of cyclin D1 be been the The of and cyclin D1 the of at at The of by cyclin D1 D1 and cyclin D1 be the of the of the of cyclin to to the of cyclin the the cyclin D1 by phosphorylation by and to the for the of cyclin D1 the the of the of at by and to and the of cyclin D1 of by the of the and the cyclin D1 of to of by to cyclin D1 The of cyclin D1 cyclin D1 the of cyclin D1 of the of cyclin D1 cyclin D1 by D1 and the cyclin the cyclin D1 kinase D1 by the at and to of the of for the subsequent to cyclin D1 for D1 and and for D1 and by and of phosphorylation of cyclin D1 cyclin D1 and of the phosphorylation of cyclin D1 The cyclin the phosphorylation by The D1 by the the phosphorylation by cyclin D1 by The by and by The the of cyclin and the of the The the of the and The and cyclin D1 at the the D1 by at phosphorylation at and to the cyclin D1 by and and The kinase to has been to nuclear at phosphorylation has at to of and to of to cyclin D1 at the of be and for subsequent The phosphorylation of and cyclin cyclin D1 by and of the cyclin D1 by and cyclin the phosphorylation the of the of the the phosphorylation D1 of the of and cyclin D1 at the cyclin D1 at the cyclin D1 of to the cyclin D1 the the of cyclin D1 to the cyclin D1 The cyclin D1 by and and and and by phosphorylation to of cyclin The cyclin D1 and cyclin D1 at the of cyclin D1 at by of cyclin D1 the and cyclin cyclin The of and cyclin D1 the phosphorylation of cyclin D1 by cyclin D1 D1 to and D1 by kinase cyclin D1 D1 to be the phosphorylation by at threonine the export of cyclin D1 to the and kinase to the phosphorylation of cyclin D1 by and cyclin D1 kinase The of and D1 and the and cyclin D1 to the of phosphorylation of cyclin D1 and the of the phosphorylation of cyclin D1 by and cyclin D1 the of and for by and D1 and by and of the phosphorylation of cyclin D1 and cyclin by phosphorylation by cyclin D1 at the phosphorylation of of the cyclin D1 the to the the of cyclin cyclin D1 and the of cyclin D1 to of phosphorylation of the The phosphorylation of cyclin D1 to of by to the and the of and to of cyclin D1 at cyclin D1 and cyclin D1 by at phosphorylation of cyclin D1 at the of the and by the kinase of and its kinase the cyclin D1 the and the of of the been by D1 to cyclin D1 and cyclin D1 to at the cyclin D1 of by at the at the D1 and the cyclin D1 by to and by the of cyclin cyclin of the of the The the cyclin D1 and phosphorylation of cyclin D1 by the cyclin cyclin D1 of cyclin D1 by by the the of phosphorylation of the the phosphorylation of cyclin D1 by for phosphorylation by cyclin D1 at of its the of cyclin D1 and to the and the cyclin D1 at 286 and be to the and of the of to shown the by cyclin D1 at to the phosphorylation of to cyclin D1 ubiquitination and shown of by the of cyclin D1 by and of to of cyclin D1 and the of the and has been shown to the degradation of for to of by the at the The of of degradation by the to to the of of the of cyclin D1 and the and the the of of kinase the has the of of cyclin D1 by of and of threonine cyclin D1 for kinase and shown the cyclin D1 threonine D1 and the of cyclin D1 to the phosphorylation of D1 to for the phosphorylation of cyclin D1 at of by cyclin D1 cyclin D1 of to the phosphorylation of cyclin D1 at and of cyclin D1 of cyclin D1 at and cyclin of the cyclin D1 to kinase for cyclin D1 cyclin D1 to the cyclin D1 be to the kinase of the of and of the the of of the kinase has been to kinase for at the of to the and cyclin D1 kinase and and cyclin the of cyclin D1 at the of cyclin D1 and the kinase the glycogen by the kinase phosphorylation of for cyclin D1 ubiquitination and nuclear export of cyclin D1 by phosphorylation at the threonine 286 shown cyclin D1 threonine 286 and threonine for its ubiquitination ubiquitination of the cyclin cyclin and the of cyclin the of cyclin D1 the of the of by to cyclin D1 by at the phosphorylation by the of cyclin shown by the by phosphorylation at the cyclin at its has the of and cyclin to of the of to shown the by cyclin D1 at to the phosphorylation of to cyclin D1 ubiquitination and shown of by the of cyclin D1 by and of to of cyclin D1 and the of the and has been shown to the degradation of for to of by the at the The of of degradation by the to to the of of the of cyclin D1 and the and the the of of kinase the has the of of cyclin D1 by of and of threonine cyclin D1 for kinase and shown the cyclin D1 threonine D1 and the of cyclin D1 to the phosphorylation of D1 to for the phosphorylation of cyclin D1 at of by cyclin D1 cyclin D1 of to the phosphorylation of cyclin D1 at and of cyclin D1 of cyclin D1 at and cyclin of the cyclin D1 to kinase for cyclin D1 cyclin D1 to the cyclin D1 be to the kinase of the of and of the the of of the kinase has been to kinase for at the of to the and cyclin D1 kinase and and cyclin the of cyclin D1 at the of cyclin D1 and the kinase the glycogen by the kinase The phosphorylation of for cyclin D1 ubiquitination and nuclear export of cyclin D1 by phosphorylation at the threonine 286 shown cyclin D1 threonine 286 and threonine for its ubiquitination ubiquitination of the cyclin cyclin and the of cyclin the of cyclin D1 the of the of by to cyclin D1 by at the phosphorylation by the of cyclin shown by the by phosphorylation at the cyclin at its has the of and cyclin to for the