Mdm2 targets the p53 transcription cofactor JMY for degradation

Coutts, Amanda S.; Boulahbel, Houda; Graham, Anne; Thangué, Nicholas B. La

doi:10.1038/sj.embor.7400855

Cited by 68 publications

(116 citation statements)

References 25 publications

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“…Both the Rb-E2F1 complex and the free E2F1 are essential for maximal induction of apoptosis [16]. Levels of JMY protein increases in cells treated "in vitro" with DNA damaging compounds like ultraviolet light`, etoposide and actinomycin D [5]. This Jmy transcription and JMY protein accumulation are induced by the transcription of E2F1 that occur due to the DNA damage [17].…”

Section: Jmy Regulation By E2f1mentioning

confidence: 99%

“…Levels of JMY protein are also subject to regulation by MDM2 in stressfree cells. JMY and MDM2 physically interact through the C-terminal domain of MDM2 which habours E3 ligase [5]. Appropriate ubiquitylation of JMY requires intact E3 ligase.…”

Section: Jmy Regulation By Mdm2mentioning

confidence: 99%

“…MDM2 for instance is a major negative regulator of p53 and its regulatory capacity can be by direct p53 ubiquitination targeting it for degradation or indirectly via p53 cofactors ubiquitination also marking them for degradation [5,7]. MDM2 further negatively regulates p53 through its E3 ubiquitin ligase activity that promotes proteasome-dependent p53 degradation and modulates nuclear export of p53 [2] .…”

Section: Introductionmentioning

confidence: 99%

“…The activity of p53 is tightly controlled and regulated at multiple levels and the importance of co-factors that influence these regulations is becoming increasingly evident (Figure 1) [5]. MDM2 for instance is a major negative regulator of p53 and its regulatory capacity can be by direct p53 ubiquitination targeting it for degradation or indirectly via p53 cofactors ubiquitination also marking them for degradation [5,7].…”

Section: Introductionmentioning

confidence: 99%

“…This process enables p53 to bind and activate proapoptotic genes. It is highly speculated that p53 selectively activates transcription of pro-apoptotic target genes upon interaction with transcriptional co-activators such as p300/CREB-binding protein (p300/CBP), Junctional and regulatory protein(JMY), Stress responsive activator of p53 (Strap) and Apoptosis-stimulating protein of p53 (ASPP) [2,5].…”

Section: Introductionmentioning

confidence: 99%

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The Role of JMY in p53 Regulation.

Adighibe¹

2018

Preprint

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Abstract:Following the event of DNA damage the levels of tumour suppressor protein p53 increases inducing either cell cycle arrest or apoptosis. Junctional Mediating and Regulating Y protein (JMY) is a transcription co-factor involved in p53 regulation. Hence in the event of DNA damage, JMY levels are also upregulated in the nucleus where JMY forms a complex with p300/CREB-binding protein (p300/CBP), Apoptosis-stimulating protein of p53 (ASPP) and Stress responsive activator of p53 (Strap). This co-activator complex then binds to and increases the ability of p53 to induce transcription of proteins triggering apoptosis but not cell cycle arrest. This then suggests that the increase of JMY levels due to DNA damage putatively "direct" p53 activity toward triggering apoptosis. JMY expression is also linked to increased cell motility as it: downregulates the expression of adhesion molecules of the Cadherin family and induces actin nucleation; making cells less adhesive and more mobile, favouring metastasis.All these characteristics taken together imply that JMY therefore possesses both tumour suppressive and tumour promoting capabilities.

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Section: Jmy Regulation By E2f1mentioning

confidence: 99%

Section: Jmy Regulation By Mdm2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Role of JMY in p53 Regulation.

Adighibe¹

2018

Preprint

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Effect of astrocyte‐targeted production of IL‐6 on traumatic brain injury and its impact on the cortical transcriptome

Quintana

Molinero

Borup

et al. 2007

Developmental Neurobiology

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Interleukin-6 (IL-6) is one of the key players in the response of the brain cortex to injury. We have described previously that astrocyte-driven production of IL-6 (GFAP-IL6) in transgenic mice, although causing spontaneous neuroinflammation and long term damage, is beneficial after an acute (freeze) injury in the cortex, increasing healing and decreasing oxidative stress and apoptosis. To determine the transcriptional basis for these responses here we analyzed the global gene expression profile of the cortex, at 0 (unlesioned), 1 or 4 days post lesion (dpl), in both GFAP-IL6 mice and their control littermates. GFAP-IL6 mice showed an increase in genes associated with the inflammatory response both at 1 dpl (Iftm1, Endod1) and 4 dpl (Gfap, C4b), decreased expression of proapoptotic genes (i.e. Gadd45b, Clic4, p21) as well as reduced expression of genes involved in the control of oxidative stress (Atf4). Furthermore, the presence of IL-6 altered the expression of genes involved in hemostasis (Vwf), cell migration and proliferation (Cap2), and synaptic activity (Vamp2). All these changes in gene expression could underlie the phenotype of the GFAP-IL6 mice after injury, but many other possible factors were also identified in this study, highlighting the utility of this approach for deciphering new pathways orchestrated by IL-6.

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Developmental expression ofDrosophilaWiskott‐Aldrich Syndrome family proteins

Rodriguez-Mesa

Abreu-Blanco

Rosales-Nieves

et al. 2012

Developmental Dynamics

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Background Wiskott-Aldrich Syndrome (WASP) family proteins participate in many cellular processes involving rearrangements of the actin cytoskeleton. To the date, four WASP subfamily members have been described in Drosophila: Wash, WASp, SCAR, and Whamy. Wash, WASp, and SCAR are essential during early Drosophila development where they function in orchestrating cytoplasmic events including membrane-cytoskeleton interactions. A mutant for Whamy has not yet been reported. Results We generated monoclonal antibodies that are specific to Drosophila Wash, WASp, SCAR, and Whamy, and use these to describe their spatial and temporal localization patterns. Consistent with the importance of WASP family proteins in flies, we find that Wash, WASp, SCAR, and Whamy are dynamically expressed throughout oogenesis and embryogenesis. For example, we find that Wash accumulates at the oocyte cortex. WASp is highly expressed in the PNS, while SCAR is the most abundantly expressed in the CNS. Whamy exhibits an asymmetric subcellular localization that overlaps with mitochondria and is highly expressed in muscle. Conclusion All four WASP family members show specific expression patterns, some of which reflect their previously known roles and others revealing new potential functions. The monoclonal antibodies developed offer valuable new tools to investigate how WASP family proteins regulate actin cytoskeleton dynamics.

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Mdm2 targets the p53 transcription cofactor JMY for degradation

Cited by 68 publications

References 25 publications

The Role of JMY in p53 Regulation.

The Role of JMY in p53 Regulation.

Effect of astrocyte‐targeted production of IL‐6 on traumatic brain injury and its impact on the cortical transcriptome

Developmental expression ofDrosophilaWiskott‐Aldrich Syndrome family proteins

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