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Hepatoma up-regulated protein (HURP)...

Wong, Jim Y.

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Hepatoma up-regulated protein (HURP) controls microtubule dynamics and spindle function.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Hepatoma up-regulated protein (HURP) controls microtubule dynamics and spindle function./
作者:	Wong, Jim Y.
面頁冊數:	191 p.
附註:	Adviser: Guowei Fang.
Contained By:	Dissertation Abstracts International67-09B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3235377
ISBN:	9780542896149

Hepatoma up-regulated protein (HURP) controls microtubule dynamics and spindle function.
Wong, Jim Y.

Hepatoma up-regulated protein (HURP) controls microtubule dynamics and spindle function. - 191 p.

Adviser: Guowei Fang.

Thesis (Ph.D.)--Stanford University, 2006.

Proper chromosome alignment at the metaphase plate ensures the fidelity of chromosome segregation in mitosis. This process of bipolar spindle formation and chromosome congression is mediated by spindle poles, microtubules, and kinetochores. Through a search-and-capture mechanism, the centrosomes nucleate microtubules which attach to kinetochores. In a parallel pathway, the chromatin nucleates microtubules which extend toward the centrosomes to link kinetochores to the mitotic spindle poles. To ensure equal segregation of chromosomes during mitosis, the spindle checkpoint monitors both the attachment of microtubules to kinetochores and the tension generated across bi-oriented sister kinetochores. Satisfaction of these two requirements results in the degradation of the anaphase inhibitor securin, leading to anaphase onset. Thus, the spindle checkpoint controls the fidelity of chromosome separation by preventing premature anaphase initiation.

ISBN: 9780542896149Subjects--Topical Terms:

1017686
Biology, Cell.

Hepatoma up-regulated protein (HURP) controls microtubule dynamics and spindle function.
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520 $a Proper chromosome alignment at the metaphase plate ensures the fidelity of chromosome segregation in mitosis. This process of bipolar spindle formation and chromosome congression is mediated by spindle poles, microtubules, and kinetochores. Through a search-and-capture mechanism, the centrosomes nucleate microtubules which attach to kinetochores. In a parallel pathway, the chromatin nucleates microtubules which extend toward the centrosomes to link kinetochores to the mitotic spindle poles. To ensure equal segregation of chromosomes during mitosis, the spindle checkpoint monitors both the attachment of microtubules to kinetochores and the tension generated across bi-oriented sister kinetochores. Satisfaction of these two requirements results in the degradation of the anaphase inhibitor securin, leading to anaphase onset. Thus, the spindle checkpoint controls the fidelity of chromosome separation by preventing premature anaphase initiation.
520 $a Disruption of mitotic events such as spindle formation and checkpoint response can promote genomic instability. Therefore, an understanding of mitotic regulation is central to dissecting the basic mechanisms of tumorigenesis. Through a genomics-based screen of the human transcriptome, hepatoma up-regulated protein (HURP) was identified as a transcript that co-varies with proteins with mitotic functions and is upregulated during the cell cycle in G2/M, suggesting that it may play a role in mitosis. siRNA-mediated depletion of HURP in metaphase cells generated unaligned chromosomes unattached to microtubules and chromosomes under partial tension. Although these defects transiently activated the spindle assembly checkpoint, HeLa cells bypassed the arrest and initiated anaphase without complete chromosome congression or proper tension. Thus, HURP is required for efficient kinetochore capture and chromosome congression, generating proper tension, and promoting timely mitotic progression.
520 $a As a microtubule-binding protein, HURP colocalizes with chromatin-proximal spindle microtubules and is required for proper spindle morphology. Mechanistically, HURP stabilizes the mitotic spindle, enhances de novo microtubule polymerization, and promotes bipolar spindle formation by reducing the turnover rate of alpha/beta-tubulin heterodimers on the spindle. These activities are regulated by the Ran pathway, which may both activate and disinhibit HURP for binding to microtubules. Also, Aurora A phosphorylation enhances the binding of HURP to microtubules. Thus, these two pathways control HURP as a key regulator of microtubule dynamics responsible proper spindle function.
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