Lineage specific composition of cyclin D- @entity11953 / @entity11954 - XXXX complexes reveals distinct functions of @entity11953 , @entity11954 and individual D-type cyclins in differentiating cells of embryonic origin.

@entity1896 @entity11954 @entity36450 @entity7919 @entity7000 @entity19 @entity6834 @entity5206 @entity189 @entity11953 @entity43679 @entity17068
OBJECTIVES: This article is to study the role of G(1)/S regulators in differentiation of pluripotent embryonic cells. MATERIALS AND METHODS: We established a @entity7000 @entity189 cell-based experimental system, which profits from two similar differentiation protocols producing endodermal or neuroectodermal lineages. The levels, mutual interactions, activities, and localization of G(1)/S regulators were analysed with respect to growth and differentiation parameters of the cells. RESULTS AND CONCLUSIONS: We demonstrate that proliferation parameters of differentiating cells correlate with the activity and structure of @entity5206 /E- @entity17068 but not of cyclin D- @entity36450 - @entity7919 complexes. In an exponentially growing @entity7000 cell population, the @entity1896 - @entity11953 complex is detected, which is replaced by @entity6834 /3- @entity36450 - @entity7919 complex following density arrest. During endodermal differentiation kinase-inactive @entity6834 /D3- @entity11953 - @entity7919 complexes are formed. Neural differentiation specifically induces @entity1896 at the expense of @entity43679 and results in predominant formation of @entity1896 /D2- @entity11953 - @entity7919 complexes. Differentiation is accompanied by cytoplasmic accumulation of cyclin Ds and @entity36450 , which in neural cells are associated with neural outgrowths. Most phenomena found here can be reproduced in @entity19 embryonic stem cells. In summary, our data demonstrate (i) that individual cyclin D isoforms are utilized in cells lineage specifically, (ii) that fundamental difference in the function of @entity11953 and @entity11954 exists, and (iii) that cyclin D- @entity36450 complexes function in the cytoplasm of differentiated cells. Our study unravels another level of complexity in G(1)/S transition-regulating machinery in early embryonic cells.
