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Biological function of the LxCxE-bin...

Bergseid, Jacqueline.

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Biological function of the LxCxE-binding pocket of retinoblastoma protein.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Biological function of the LxCxE-binding pocket of retinoblastoma protein./
作者:	Bergseid, Jacqueline.
面頁冊數:	136 p.
附註:	Advisers: Jean Y. J. Wang; Randall S. Johnson.
Contained By:	Dissertation Abstracts International67-12B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3244732

Biological function of the LxCxE-binding pocket of retinoblastoma protein.
Bergseid, Jacqueline.

Biological function of the LxCxE-binding pocket of retinoblastoma protein. - 136 p.

Advisers: Jean Y. J. Wang; Randall S. Johnson.

Thesis (Ph.D.)--University of California, San Diego, 2007.

The product of the retinoblastoma gene (pRb) is a tumor suppressor protein that regulates cellular proliferation, apoptosis and differentiation of numerous tissues in mice. It contains multiple peptide-binding pockets through which it interacts with a host of cellular and viral proteins. The LxCxE-binding pocket of pRb has been highly conserved between pRb proteins from evolutionary distant species; however, the in vivo function of this binding pocket is unknown. The crystal structure of pRB bound to LxCxE peptide was used to design a single point mutation, N757F, which specifically inactivates interactions between pRB and LxCxE-containing proteins without affecting the pRB-E2F interaction. The N750F mutation (analogous to N757F in the human RB) was introduced into the mouse Rb-1 locus by homologous recombination. The RbN750F/N750F mice do not exhibit the phenotype of embryonic lethality observed in Rb-null mice. The pRb-N750F protein does not co-immunoprecipitate with E1A, demonstrating disruption of the LxCxE-binding pocket. The Rb+/- mice develop pituitary tumors with 90% penetrance through LOH. By contrast, the pRb-N750F protein retains its pituitary tumor suppression function as evidenced by the lack of pituitary tumors in RbN750F/N750F and Rb+/N750F mice. This is consistent with the data from tissue culture experiments demonstrating that RbN750F/N750F fibroblasts do not exhibit any cell cycle defects.Subjects--Topical Terms:

1017686
Biology, Cell.

Biological function of the LxCxE-binding pocket of retinoblastoma protein.
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035 $a (UMI)AAI3244732
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040 $a UMI $c UMI
100 1 $a Bergseid, Jacqueline. $3 1287170
245 1 0 $a Biological function of the LxCxE-binding pocket of retinoblastoma protein.
300 $a 136 p.
500 $a Advisers: Jean Y. J. Wang; Randall S. Johnson.
500 $a Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 6852.
502 $a Thesis (Ph.D.)--University of California, San Diego, 2007.
520 $a The product of the retinoblastoma gene (pRb) is a tumor suppressor protein that regulates cellular proliferation, apoptosis and differentiation of numerous tissues in mice. It contains multiple peptide-binding pockets through which it interacts with a host of cellular and viral proteins. The LxCxE-binding pocket of pRb has been highly conserved between pRb proteins from evolutionary distant species; however, the in vivo function of this binding pocket is unknown. The crystal structure of pRB bound to LxCxE peptide was used to design a single point mutation, N757F, which specifically inactivates interactions between pRB and LxCxE-containing proteins without affecting the pRB-E2F interaction. The N750F mutation (analogous to N757F in the human RB) was introduced into the mouse Rb-1 locus by homologous recombination. The RbN750F/N750F mice do not exhibit the phenotype of embryonic lethality observed in Rb-null mice. The pRb-N750F protein does not co-immunoprecipitate with E1A, demonstrating disruption of the LxCxE-binding pocket. The Rb+/- mice develop pituitary tumors with 90% penetrance through LOH. By contrast, the pRb-N750F protein retains its pituitary tumor suppression function as evidenced by the lack of pituitary tumors in RbN750F/N750F and Rb+/N750F mice. This is consistent with the data from tissue culture experiments demonstrating that RbN750F/N750F fibroblasts do not exhibit any cell cycle defects.
520 $a The lack of embryonic lethality in RbN750F/N750F mice allowed us to study the effect of this mutation on adult tissues. The RbN750F/N750F mice have elevated levels of platelets and lymphocytes in the peripheral blood. The RbN750F/N750F females are infertile due to anovulation. These findings demonstrate for the first time that the LxCxE-binding pocket of pRb plays a role in thromobopoiesis, lymphopoiesis and ovulation. The Rb N750F/- mice are born at the frequency of 13% and die by the age of 8 months, indicating that, unlike Rb+ allele, the RbN750F allele is haploinsufficient. The RbN750F/- females are also infertile due to the lack of FSH and LH function in the ovaries.
590 $a School code: 0033.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Genetics. $3 1017730
690 $a 0369
690 $a 0379
710 2 0 $a University of California, San Diego. $3 1018093
773 0 $t Dissertation Abstracts International $g 67-12B.
790 $a 0033
790 1 0 $a Johnson, Randall S., $e advisor
790 1 0 $a Wang, Jean Y. J., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3244732