The Positive Regulation of p53 by the Tumor Suppressor VHL

Roe, Jae Seok; Youn, Hong Duk

doi:10.4161/cc.5.18.3247

Cited by 52 publications

(47 citation statements)

References 29 publications

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“…Dysfunction of each of these proteins is responsible for aneuploidy. Moreover both pVHL and Aurora A were shown to interact, respectively, with the p53 protein, a cell cycle regulator p53 protein (Roe et al 2006). In addition, their presence in molecular complexes together with the tumor suppressor protein p53 would also be related by another way to their involvement in cell cycle progression and tumorigenesis (Fu et al 2007).…”

Section: Discussionmentioning

confidence: 99%

“…It is an E3 ubiquitin protein ligase involved in the ubiquitin proteasome pathway to degrade the endogenous proteins (E3 targets the protein substrates for specific degradation by the proteasome). This tumor suppressor controls also the cell cycle (Roe et al 2006), participates in the development and stability of the mitotic spindle (Hergovich et al 2003;Lolkema et al 2004) and mediates the functioning of centrosomes (Kuehn et al 2007). The tumor suppressor pVHL plays a role in chromosome stability (Roe et al 2006) and its absence increases aneuploidy.…”

Section: Introductionmentioning

confidence: 99%

“…This tumor suppressor controls also the cell cycle (Roe et al 2006), participates in the development and stability of the mitotic spindle (Hergovich et al 2003;Lolkema et al 2004) and mediates the functioning of centrosomes (Kuehn et al 2007). The tumor suppressor pVHL plays a role in chromosome stability (Roe et al 2006) and its absence increases aneuploidy. Moreover it is involved in the stabilization of the p53 protein (Roe et al 2006) and regulates the tumor growth and cytokinesis (Thoma et al 2009;Sinha et al 2011).…”

Section: Introductionmentioning

confidence: 99%

“…The tumor suppressor pVHL plays a role in chromosome stability (Roe et al 2006) and its absence increases aneuploidy. Moreover it is involved in the stabilization of the p53 protein (Roe et al 2006) and regulates the tumor growth and cytokinesis (Thoma et al 2009;Sinha et al 2011).…”

Section: Introductionmentioning

confidence: 99%

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Aurora A kinase interacts with and phosphorylates VHL protein

Ferchichi¹,

Arlot²,

Cremet³

et al. 2012

Biologia

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Abstract:The serine/threonin kinase Aurora A is an oncoprotein, whereas von Hippel-Lindau protein (pVHL) is a tumor suppressor protein. Both proteins have the same localization during mitosis: in the mitotic spindle and the centrosome. These two proteins also have common functions, such as the regulation of the cell cycle, the stability of the mitotic spindle and both intervene in the functioning of centrosomes. In this study we have analyzed the interaction between Aurora A and pVHL with immunoprecipitation and in vitro phosphorylation experiments. We have confirmed that the immunoprecipitation of pVHL from Hek 293 cell extracts were coupled with Aurora A. In addition, the interaction between the two proteins has been tested by analyzing the phosphorylation of pVHL in vitro by Aurora A. The results revealed that pVHL was phosphorylated by Aurora A. In conclusion, the study demonstrated that Aurora A interacts with and phosphorylates pVHL. Given the role of these two proteins in cell division as well as their status in cancer, this interaction requires further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Aurora A kinase interacts with and phosphorylates VHL protein

Ferchichi¹,

Arlot²,

Cremet³

et al. 2012

Biologia

View full text Add to dashboard Cite

show abstract

“…Two p53 binding sites were identified within the HIF-1· oxygen dependent degradation domain (12,13). Additionally, pVHL, a negative regulator of HIF-1· stabilization, associates directly with p53 by inhibiting Hdm2-mediated ubiquitinylation (14). The p53 protein is modified through multiple posttranslational events, including phosphorylation and acetylation.…”

Section: Introductionmentioning

confidence: 99%

TCDD mediates inhibition of p53 and activation of ERα signaling in MCF-7 cells at moderate hypoxic conditions

Seifert

Täubert²,

Hombach‐Klonisch³

et al. 2009

Int J Oncol

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Abstract. TCDD (2,3,7, is known to promote cancer initiation and progression and accumulates in mammary fat tissue. Effects of TCDD are mediated by the aryl hydrocarbon receptor (AhR). Physiological conditions of moderate hypoxia in breast cancer also activate another transcription factor, hypoxia-inducible factor-1 alpha (HIF-1·). In addition, the transcription factors p53 and the estrogen receptor alpha (ER·) are important key players in breast cancer progression. Here, human breast cancer cells cultured under mild hypoxic conditions were exposed to TCDD and analyzed for regulation of p53 signaling and ER· transactivation. Simultaneous exposure to TCDD and hypoxia resulted in a moderate but reproducible inhibition of p53 expression. Both the direct activation of the ER· and the transcriptional regulation of Hdm2 mediated this inhibition. As consequence the p53-mediated target gene expression (Dusp5) was reduced. Silencing of Dusp5 by simultaneous exposure of TCDD and hypoxia or by RNAi led to increased phosphorylation of ERK1/2. This increase resulted in transactivation of ER· and induction of ER·-mediated transcription of Hdm2 and SOCS3. Specificity of ER·-transactivation by ERK1/2 was confirmed by treatment with MAPKK-inhibitor PD98059. The combination of inhibition of functional p53 protein and induction of ER· signaling could serve as a model for the operational sequence of TCDD effects to prevent cell death and promote breast tumor progression.

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Building it up and taking it down: The regulation of vertebrate ciliogenesis

Santos

Reiter

2008

Developmental Dynamics

111

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Primary cilia project from the surface of most vertebrate cells, and function in sensation and signaling during both development and adult tissue homeostasis. Mounting evidence links ciliary defects with a wide variety of diseases, underscoring the importance of understanding how these dynamic organelles are assembled and maintained. However, despite their physiological and clinical relevance, the logic and machinery that regulate ciliogenesis remain largely enigmatic. Here, we summarize emerging data that connect the assembly and disassembly of the primary cilium to cell cycle progression and we examine how determinants of cell architecture, including the planar cell polarity pathway, may regulate ciliogenesis. Additionally, identification of the genes underlying diverse ciliopathies in human patients is shedding light on the regulation of the formation of this complex organelle.

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The Positive Regulation of p53 by the Tumor Suppressor VHL

Abstract: Previously published online as a Cell Cycle E-publication: http://www.landesbioscience.com/journals/cc/abstract.php?id=3247 KEY WORDSvon Hippel-Lindau, p53, tumor suppressor, ATM, histone acetyltransferase, transactivation ACKNOWLEDGEMENTS

Cited by 52 publications

References 29 publications

Aurora A kinase interacts with and phosphorylates VHL protein

Aurora A kinase interacts with and phosphorylates VHL protein

TCDD mediates inhibition of p53 and activation of ERα signaling in MCF-7 cells at moderate hypoxic conditions

Building it up and taking it down: The regulation of vertebrate ciliogenesis

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