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You searched for +publisher:"University of North Carolina" +contributor:("He, Yizhou"). One record found.

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University of North Carolina

1. He, Yizhou. Identification of Novel Regulatory and Target Proteins in the p53 Pathway: APC2 and PFK2.

Degree: 2014, University of North Carolina

The Mdm2 proto-oncoprotein is the primary negative regulator for the tumor suppressor p53. While it is believed that Mdm2 degradation is regulated via its own E3 ubiquitin ligase activity, recent development of knock-in mouse models demonstrate that in vivo Mdm2 E3 ligase function is dispensable for the degradation of Mdm2 itself. Here, we show that the anaphase promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase for Mdm2 degradation. We demonstrate that APC2, a scaffold subunit of APC/C, binds to Mdm2 and is required for Mdm2 polyubiquitination and proteasomal degradation. Downregulation of APC2 by RNAi results in transcription-independent accumulation of Mdm2 and attenuation of stress-induced p53 stabilization, leading to decreased senescence and increased cell survival. Furthermore, APC2 expression is frequently downregulated in human cancers and in tumor cell lines, and often correlates with Mdm2 overexpression. Our study shows the regulation of Mdm2 by APC/C E3 ubiquitin ligase, modifying our understanding of Mdm2 degradation in vivo, and providing important therapeutic implications for tumors with Mdm2 overexpression. Although nucleotide shortage can result in genomic instability and cancer development, relatively little is known regarding the mechanisms responsible for coordinating nucleotide shortage and cell metabolism to maintain a nucleotide pool amenable to DNA replication and DNA damage repair. Here, we provide evidence supporting a model whereby p53-dependent regulation of phosphofructokinase-2 (PFK2) is essential for the redirection of glucose from glycolysis to the pentose phosphate pathway (PPP) under nucleotide shortage stress. Our data show that the suppression of PFK2 is specific to nucleotide shortage. Decreased expression of PFK2 resulted in a decrease in the rate of glycolysis and an increase in PPP activity, leading to an increased nucleotide pool and improved DNA damage repair efficiency. Importantly, exogenously supplied nucleosides effectively rescued the DNA damage repair defect caused by p53 inactivation, further suggesting that the maintenance of the nucleotide pool is an important function of p53. These findings underscore an essential role for p53 in modulating glucose metabolism in response to nucleotide shortage stress, and suggest that the tumor suppressive function of p53 is linked to its role in responding to nucleotide shortage and coordinating metabolic adaptation. Advisors/Committee Members: He, Yizhou, Zhang, Yanping, Marzluff, William, Zhang, Yanping, Marzluff, William, Xiong, Yue, Cox, Adrienne, Dittmer, Dirk.

Subjects/Keywords: Biology; Genetics; Molecular biology; School of Medicine; Curriculum in Genetics and Molecular Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

He, Y. (2014). Identification of Novel Regulatory and Target Proteins in the p53 Pathway: APC2 and PFK2. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:aeef9369-e7e6-440c-834d-19401d853820

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

He, Yizhou. “Identification of Novel Regulatory and Target Proteins in the p53 Pathway: APC2 and PFK2.” 2014. Thesis, University of North Carolina. Accessed August 09, 2020. https://cdr.lib.unc.edu/record/uuid:aeef9369-e7e6-440c-834d-19401d853820.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

He, Yizhou. “Identification of Novel Regulatory and Target Proteins in the p53 Pathway: APC2 and PFK2.” 2014. Web. 09 Aug 2020.

Vancouver:

He Y. Identification of Novel Regulatory and Target Proteins in the p53 Pathway: APC2 and PFK2. [Internet] [Thesis]. University of North Carolina; 2014. [cited 2020 Aug 09]. Available from: https://cdr.lib.unc.edu/record/uuid:aeef9369-e7e6-440c-834d-19401d853820.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

He Y. Identification of Novel Regulatory and Target Proteins in the p53 Pathway: APC2 and PFK2. [Thesis]. University of North Carolina; 2014. Available from: https://cdr.lib.unc.edu/record/uuid:aeef9369-e7e6-440c-834d-19401d853820

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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