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Subnuclear compartmentalization of c...

Powers, Sarah Eileen.

Subnuclear compartmentalization of cell cycle effectors in B lymphopoiesis.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Subnuclear compartmentalization of cell cycle effectors in B lymphopoiesis.
作者:	Powers, Sarah Eileen.
面頁冊數:	165 p.
附註:	Source: Dissertation Abstracts International, Volume: 72-06, Section: B, page: .
附註:	Adviser: Marcus R. Clark.
Contained By:	Dissertation Abstracts International72-06B.
標題:	Biology, Cell.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3445045
ISBN:	9781124535982

Subnuclear compartmentalization of cell cycle effectors in B lymphopoiesis.
Powers, Sarah Eileen.

Subnuclear compartmentalization of cell cycle effectors in B lymphopoiesis. - 165 p.

Source: Dissertation Abstracts International, Volume: 72-06, Section: B, page: .

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.

ISBN: 9781124535982Subjects--Topical Terms:

226967
Biology, Cell.

Subnuclear compartmentalization of cell cycle effectors in B lymphopoiesis.
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502 $a Thesis (Ph.D.)--The University of Chicago, 2011.
520 $a 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.
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