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Regulation of nuclear transport and ...
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Chen, Ting.
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Regulation of nuclear transport and mitosis by Ran GTPase.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Regulation of nuclear transport and mitosis by Ran GTPase./
作者:
Chen, Ting.
面頁冊數:
176 p.
附註:
Adviser: Ian G. Macara.
Contained By:
Dissertation Abstracts International67-10B.
標題:
Biology, Cell. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3238148
ISBN:
9780542923722
Regulation of nuclear transport and mitosis by Ran GTPase.
Chen, Ting.
Regulation of nuclear transport and mitosis by Ran GTPase.
- 176 p.
Adviser: Ian G. Macara.
Thesis (Ph.D.)--University of Virginia, 2007.
One of the hallmarks of the eukaryotic cell is the possession of a nuclear envelope. Transport of macromolecules between the nuclear and cytoplasmic compartments is mainly regulated by the small GTPase, Ran. The nucleotide exchange factor RCC1 catalyzes formation of RanGTP, whereas the hydrolysis of RanGTP is stimulated by RanGAP1 and RanBP1. Because RCC1 is chromatin-bound throughout the cell cycle while RanGAP1 and RanBP1 are cytoplasmic, the concentration of RanGTP is high near the chromatin. This RanGTP gradient is essential for many cellular processes, including nuclear transport during interphase, mitotic spindle formation, and nuclear envelope assembly during mitosis.
ISBN: 9780542923722Subjects--Topical Terms:
1017686
Biology, Cell.
Regulation of nuclear transport and mitosis by Ran GTPase.
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One of the hallmarks of the eukaryotic cell is the possession of a nuclear envelope. Transport of macromolecules between the nuclear and cytoplasmic compartments is mainly regulated by the small GTPase, Ran. The nucleotide exchange factor RCC1 catalyzes formation of RanGTP, whereas the hydrolysis of RanGTP is stimulated by RanGAP1 and RanBP1. Because RCC1 is chromatin-bound throughout the cell cycle while RanGAP1 and RanBP1 are cytoplasmic, the concentration of RanGTP is high near the chromatin. This RanGTP gradient is essential for many cellular processes, including nuclear transport during interphase, mitotic spindle formation, and nuclear envelope assembly during mitosis.
520
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During the initial phase of my project I examined the nucleocytoplasmic shuttling of an unusual protein called JAZ, which does not contain classical dsRNA binding domains but instead binds RNA with high affinity through C2H2 zinc fingers. I showed that JAZ is a nuclear protein at steady state but is highly dynamic within the nucleus and undergoes nucleocytoplasmic shuttling. JAZ associates with Exp-5 in the presence of RanGTP and a hairpin RNA, and nuclear export of JAZ requires Exp-5. However, JAZ also binds to ILF3, in an RNA-independent manner, and JAZ and ILF3 can form a heteromeric complex with Exp-5 and RanGTP. Unlike ILF3, JAZ does not contain a classical NLS. In principle it could diffuse passively through the nuclear pores, and I showed that import is indeed independent of soluble transport factors. However, import is inhibited by wheat germ agglutinin and by low temperatures, which do not inhibit passive diffusion.
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In the second phase of my project, I discovered a unique modification on RCC1, in which the N-terminal Ser/Pro residue of mammalian RCC1 is methylated on its alpha-amino group. A methyltransferase activity for N-terminal methylation of RCC1 is present in soluble nuclear extracts from HeLa cells. Methylation-defective mutants of RCCI are unable to bind as effectively as wild type protein to chromatin during mitosis, which results in supernumerary centrosomes and spindle formation defects. These defects are additive to those caused by a mutation that disrupts exchange activity, and may result from decreased binding to DNA. Coupling RCC1 to histone H2A, to force chromatin attachment, reverses the mitotic defects.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3238148
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