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作者 Powers, Sarah Eileen
書名 Subnuclear compartmentalization of cell cycle effectors in B lymphopoiesis
國際標準書號 9781124535982
book jacket
說明 165 p
附註 Source: Dissertation Abstracts International, Volume: 72-06, Section: B, page:
Adviser: Marcus R. Clark
Thesis (Ph.D.)--The University of Chicago, 2011
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 lymphopoiesis
School code: 0330
Host Item Dissertation Abstracts International 72-06B
主題 Biology, Cell
Health Sciences, Immunology
Alt Author The University of Chicago. Immunology
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