Ubiquitin-Dependent Distribution of the Transcriptional Coactivator p300 in Cytoplasmic Inclusion Bodies

Chen, Jihong; Halappanavar, Sabina; ng, Th'; Li, Qiao

doi:10.4161/epi.2.2.4326

Cited by 27 publications

(25 citation statements)

References 48 publications

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“…Our study, using a cytoplasmic-restricted p53 NLS mutant (23), has shown that p53 acetylation can take place in the cytoplasm very efficiently. This should not be surprising given that p300/CBP, the acetyltransferase for p53, can be found in both the nucleus and the cytoplasm (28) and was recently shown to be a shuttling protein (29). On the other hand, the possibility that the cytoplasmic localized p53 could be acetylated by a yet-unidentified acetyltransferase cannot be excluded.…”

Section: Discussionmentioning

confidence: 84%

p53 Oligomerization Is Essential for Its C-terminal Lysine Acetylation

Itahana

Zhang

2009

Journal of Biological Chemistry

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Acetylation of multiple lysine residues in the p53 plays critical roles in the protein stability and transcriptional activity of p53. To better understand how p53 acetylation is regulated, we generated a number of p53 mutants and examined acetylation of each mutant in transfected cells. We found that p53 mutants that are defective in tetramer formation are also defective in C-terminal lysine residue acetylation. Consistently, we found that several cancer-derived p53 mutants that bear mutations in the tetramerization domain cannot form oligomers and are defective in C-terminal lysine acetylation, and these mutants are inactive in p21 transactivation. We demonstrated that the acetyltransferase p300 interacts with and promotes acetylation of wild-type p53 but not with any of the artificially generated or human cancer-derived p53 mutants that are defective in oligomerization. These results, combined with a computer-aided crystal structure analysis, suggest a model in which p53 oligomerization precedes its acetylation by providing docking sites for acetyltransferases.

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Section: Discussionmentioning

confidence: 84%

p53 Oligomerization Is Essential for Its C-terminal Lysine Acetylation

Itahana

Zhang

2009

Journal of Biological Chemistry

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“…GRAIL and hepatic nutrient metabolism 2005, Chen et al 2007, Dentin et al 2007, Sano et al 2007, Kato et al 2008. GRAIL might also affect the expression of genes related to glucose production through the ubiquitination of such transcriptional regulators.…”

Section: Discussionmentioning

confidence: 99%

Role of the E3 ubiquitin ligase gene related to anergy in lymphocytes in glucose and lipid metabolism in the liver

Nakamichi¹,

Senga²,

Inoue³

et al. 2008

Journal of Molecular Endocrinology

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Gene related to anergy in lymphocytes (GRAIL) is an E3 ubiquitin ligase that regulates energy in T-lymphocytes. Whereas, the relevance of GRAIL to T lymphocyte function is well established, the role of this protein in other cell types remains unknown. Given that GRAIL is abundant in the liver, we investigated the potential function of GRAIL in nutrient metabolism by generating mice in which the expression of GRAIL is reduced specifically in the liver. Adenovirusmediated transfer of a short hairpin RNA specific for GRAIL mRNA markedly reduced the amounts of GRAIL mRNA and protein in the liver. Blood glucose levels of the mice with hepatic GRAIL deficiency did not differ from those of control animals in the fasted or fed states. However, these mice manifested glucose intolerance in association with a normal increase in plasma insulin levels during glucose challenge. The mice also manifested an increase in the serum concentration of free fatty acids, whereas the serum levels of cholesterol and triglyceride were unchanged. The hepatic abundance of mRNAs for glucose-6-phosphatase, catalytic (a key enzyme in hepatic glucose production) and for sterol regulatory element-binding transcription factor 1 (an important transcriptional regulator of lipogenesis) was increased in the mice with hepatic GRAIL deficiency, possibly contributing to the metabolic abnormalities of these animals. Our results thus demonstrate that GRAIL in the liver is essential for maintenance of normal glucose and lipid metabolism in living animals.

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“…25 In addition, p300 is also a substrate of the cytoplasmic ubiquitin-proteasome system. 26 The ubiquitin system plays a central role in diverse cellular processes including protein homeostasis, DNA repair and immune function. 27 Dysfunction of this system leads to various pathological conditions such as cancer, neurodegenerative diseases and immunological disorders.…”

Section: Introductionmentioning

confidence: 99%