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Nuclear Pyruvate Kinase M2 Functional Study in Cancer CellsGao, Xueliang 10 August 2010 (has links)
Cancer cells take more glucose to provide energy and phosphoryl intermediates for cancer progression. Meanwhile, energy-provider function of mitochondria in cancer cells is disrupted. This phenomenon is so-called Warburg effect, which is discovered over eighty years ago. The detail mechanisms for Warburg effect are not well defined. How glycolytic enzymes contribute to cancer progression is not well known. PKM2 is a glycolytic enzyme dominantly localized in the cytosol, catalyzing the production of ATP from PEP. In this study, we discovered that there were more nuclear PKM2 expressed in highly proliferative cancer cells. The nuclear PKM2 levels are correlated with cell proliferation rates. According to our microarry analyses, MEK5 gene was upregulated in PKM2 overexpression cells. Our studies showed that PKM2 regulated MEK5 gene transcription to promote cell proliferation. Moreover, nuclear PKM2 phosphorylated Stat3 at Y705 site using PEP as a phosphoryl group donor to regulate MEK5 gene transcription. Our study also showed that double phosphorylated p68 RNA helicase at Y593/595 interacted with PKM2 at its FBP binding site. Under the stimulation of growth factors, p68 interacted with PKM2 to promote the conversion from tetrameraic to dimeric form so as to regulate its protein kinase activity. Overexpression PKM2 in less aggressive cancer cells induced the formation of multinuclei by regulating Cdc14A gene transcription. Overall, this study presents a step forward in understanding the Warburg effect.
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The Nucleocytoplasmic Shuttling Functions of P68 in Cancer Cell Migration and ProliferationWang, Haizhen 10 August 2011 (has links)
P68 RNA helicase (p68), as a DEAD family protein, is a typical RNA helicase protein. P68 functions in many other biological processes, which include the regulations of the gene transcription, cell proliferation and cell differentiation. In our group, Y593 phosphorylated p68 was found to have a function in the epithelial mesynchymal transition, which is an important process for cancer metastasis. In the present study, we found that p68 is a nucleocytoplasmic shuttling protein. The protein carries two functional nuclear exporting signal sequences and two nuclear localization signal sequences. Calmodulin, a calcium sensor protein, is well known to play roles in cell migration by regulating the activities of its target proteins at the leading edge. Calmodulin interacts with p68 at the IQ motif of p68. However, the biological function of this interaction is not known. In this study, we found that the p68/calmodulin protein complex functions as a microtubule motor in migrating cells. The shuttling function of p68 along with the motor function of p68/calmodulin causes the leading edge distribution of calmodulin in migrating cells. Disruption the interaction between p68 and calmodulin inhibits cancer cell metastasis in an established mouse model. On the other hand, Y593-Y595 double phosphorylated p68 were found to interact with PKM2, an important tumor isoform of pyruvate kinase. The shuttling function of p68 is reasoned to promote the dimer formation of PKM2 and transport the PKM2 to the cell nucleus. The nuclear PKM2 was found to function as a protein kinase to promote cell proliferation. In specific, the nuclear PKM2 phosphorylates and activates Stat3, an important transcription factor functions in cell proliferation. Overall, p68 is found to have functions in both cell migration and cell proliferation, and these two functions depend on the nucleocytoplasmic shuttling activity and the post-translational modification of p68.
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Studies on the DEAD-box RNA-helicase Dbp5 and the ABC-protein Rli1 in translation termination and identification of a novel function of Dbp5 in ribosomal transportNeumann, Bettina 20 April 2015 (has links)
No description available.
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Structural and functional studies of the spliceosomal RNP remodeling enzyme Brr2Santos, Karine 20 November 2012 (has links)
No description available.
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Mechanism of regulation of spliceosome activation by Brr2 and Prp8 and links to retinal diseaseMozaffari Jovin, Sina 08 February 2013 (has links)
No description available.
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Biophysical and Crystallographic Characterization of Spliceosomal DExD/H-box ATPasesHamann, Florian 29 August 2019 (has links)
No description available.
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Molecular Mechanism of the TRAMP ComplexJia, Huijue January 2011 (has links)
No description available.
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MECHANISM OF RNA DUPLEX UNWINDING BY THE OLIGOMERIC DEAD-BOX RNA HELICASE DED1PPutnam, Andrea A. 27 January 2016 (has links)
No description available.
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Redundant structural motifs in a unique retroviral posttranscriptional control element mediate a novel mechanism of translational enhancementRoberts, Tiffiney Marie 07 November 2003 (has links)
No description available.
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Growth-regulated expression and G0-specific turnover of the mRNA that encodes AH49, a mammalian protein highly related to the mRNA export protein UAP56Pryor, Anne M. January 2003 (has links)
No description available.
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