MARC 主機 00000nam  2200385   4500 
001    AAI3445045 
005    20111105132443.5 
008    111105s2011    ||||||||||||||||| ||eng d 
020    9781124535982 
035    (UMI)AAI3445045 
040    UMI|cUMI 
100 1  Powers, Sarah Eileen 
245 10 Subnuclear compartmentalization of cell cycle effectors in
       B lymphopoiesis 
300    165 p 
500    Source: Dissertation Abstracts International, Volume: 72-
       06, Section: B, page:  
500    Adviser: Marcus R. Clark 
502    Thesis (Ph.D.)--The University of Chicago, 2011 
520    At the pro-B to pre-B cell transition, signals through the
       pre-B cell antigen receptor and interleukin 7 receptor 
       coordinate clonal expansion of cells bearing a 
       successfully rearranged immunoglobulin heavy chain. 
       Several studies have indicated that PI3K-Akt signaling 
       downstream of these receptors enhances proliferation and 
       that this is associated with upregulation of cyclin D3 
       protein and repression of p27. However, this model has not
       been rigorously examined in vivo in the context of B 
       lymphopoiesis. Herein, we demonstrate differential usage 
       of cyclin D2 and cyclin D3 in B cell progenitors that is 
       not apparent in fibroblasts. Furthermore, proliferation is
       normal in pro-B and pre-B cells from p85alpha-/- mice and 
       decreased in PtenloxP/loxPCD19Cre+/-  mice. Subsequent 
       biochemical analyses confirmed that inhibiting PI3K led to
       a decrease in soluble cyclin D3 and an increase in p27. 
       However, that portion of each of these molecules 
       associated with the cyclin D3 binding partner CDK4 or with
       the target of this holoenzyme complex, retinoblastoma 
       protein (Rb), did not change with PI3K inhibition. In 
       addition, we detected a substantial and PI3K-independent 
       fraction of cyclin D3 associated with the nuclear matrix. 
       None of these fractions of cyclin D3 overlapped with 
       nuclear cyclin D2. These data indicate that there are at 
       least three distinct subnuclear compartments of cyclin D3 
       which are regulated by different signaling pathways and 
       which appear to have different functions during B 
590    School code: 0330 
650  4 Biology, Cell 
650  4 Health Sciences, Immunology 
690    0379 
690    0982 
710 2  The University of Chicago.|bImmunology 
773 0  |tDissertation Abstracts International|g72-06B 
856 40 |u