Rictor Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Suppressing Autophagy and Regulating MAPK Signaling

Xu, Dongwei; Zhu, Jianjun; Jeong, Seogsong; Li, Dawei; Hua, Xing; Huang, Lifeng; Zhang, Jianjun; Luo, Yong; Xia, Qiang

doi:10.1159/000488165

Cited by 18 publications

(24 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found 276 co-altered genes for both shRNAs targeting E2F4 ( Figure 6A). 18,19 The MAPK signalling pathway is also studied in AML. The MAPK signalling pathway is a classic cancer-associated signalling pathway involved in the proliferation and differentiation of tumour cells.…”

Section: Overexpression Of Ezh2 Reverses E2f4mediated Inhibition Ofmentioning

confidence: 99%

“…The MAPK signalling pathway is a classic cancer-associated signalling pathway involved in the proliferation and differentiation of tumour cells. 18,19 The MAPK signalling pathway is also studied in AML. 20,21 To determine the specific mechanism of E2F4-induced tumour cell proliferation and differentiation, we further examined the protein levels of MAPK, p-MAPK, ERK and p-ERK when E2F4 expression levels were manipulated in AML cells.…”

Section: Overexpression Of Ezh2 Reverses E2f4mediated Inhibition Ofmentioning

confidence: 99%

See 1 more Smart Citation

E2F4 functions as a tumour suppressor in acute myeloid leukaemia via inhibition of the MAPK signalling pathway by binding to EZH2

Feng

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Acute myeloid leukaemia (AML) is an aggressive and mostly incurable haematological malignancy with frequent relapse after an initial response to standard chemotherapy. Therefore, novel therapies are urgently required to improve AML clinical outcome. Here, we aim to study the dysregulation of a particular transcription factor, E2F4, and its role in the progression of AML. In this study, human clinical data from the Gene Expression Profiling Interactive Analysis (GEPIA) revealed that increased E2F4 expression was associated with poor prognosis in AML patients. Moreover, the experimental results showed that E2F4 was aberrantly overexpressed in human AML patients and cell lines. Depletion of E2F4 inhibited the proliferation, induced the differentiation and suppressed the growth of AML cells in a nude mouse model. By contrast, overexpression of E2F4 promoted the proliferation and inhibited the differentiation of AML cells in vitro. Additionally, E2F4 expression not only is positively correlated with EZH2 but also can bind to EZH2. RNA microarray results also showed that E2F4 can regulate MAPK signalling pathway. EZH2 can reverse the inhibitory effect of E2F4 silencing on MAPK signaling pathway. In summary, our data suggest that E2F4 may be a potential therapeutic target for AML therapy.

show abstract

Section: Overexpression Of Ezh2 Reverses E2f4mediated Inhibition Ofmentioning

confidence: 99%

Section: Overexpression Of Ezh2 Reverses E2f4mediated Inhibition Ofmentioning

confidence: 99%

E2F4 functions as a tumour suppressor in acute myeloid leukaemia via inhibition of the MAPK signalling pathway by binding to EZH2

Feng

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Nox4-induced oxidative stress is a pathological feature of cerebral hypoxia-ischemia 53,54 and Rictor/mTorc2 deficiency has been shown to aggravate HI-induced injury in various models 55,56 . Based on this knowledge, we aimed to verify the involvement of the Parp3-mTorc2 axis in vivo in normal mice and in response to HI.…”

Section: Enhanced Nox4-induced Ros In Parp3-deficient Cells Cause Incmentioning

confidence: 99%

Parp3 promotes astrocytic differentiation through a tight regulation of Nox4-induced ROS and mTorc2 activation

et al. 2020

View full text Add to dashboard Cite

Parp3 is a member of the Poly(ADP-ribose) polymerase (Parp) family that has been characterized for its functions in strand break repair, chromosomal rearrangements, mitotic segregation and tumor aggressiveness. Yet its physiological implications remain unknown. Here we report a central function of Parp3 in the regulation of redox homeostasis in continuous neurogenesis in mice. We show that the absence of Parp3 provokes Nox4-induced oxidative stress and defective mTorc2 activation leading to inefficient differentiation of post-natal neural stem/progenitor cells to astrocytes. The accumulation of ROS contributes to the decreased activity of mTorc2 as a result of an oxidation-induced and Fbxw7-mediated ubiquitination and degradation of Rictor. In vivo, mTorc2 signaling is compromised in the striatum of naïve post-natal Parp3-deficient mice and 6 h after acute hypoxia-ischemia. These findings reveal a physiological function of Parp3 in the tight regulation of striatal oxidative stress and mTorc2 during astrocytic differentiation and in the acute phase of hypoxia-ischemia.

show abstract

“…RICTOR is predicted to be inhibited and the inhibition of this protein has been associated to inflammatory tissue infiltration, enhanced production of ROS and regulation of proliferation (Xu et al, 2018), alterations that we described in our models.…”

Section: Western Blot Validation Of Proteomic Resultsmentioning

confidence: 63%

New insights into creatine transporter deficiency

Molinaro

2020

Premio Tesi Di Dottorato

View full text Add to dashboard Cite

Creatine (Cr) transporter deficiency (CCDS1) is a very rare and severe condition due to impaired energetic metabolism. In this work we showed for the first time the following facts: this diseases is a progressive neurodegenerative disorder in which a set of maladaptive compensatory mechanisms leads to a progressive damage of brain functions; cell energy metabolism and mitochondria seem strongly involved in the pathogenesis and they could represent useful potential targets for therapeutic interventions; inflammation seems to play an important part in this progressive damage, and this observation can pave the way to treatment strategies; neural circuits disruption involving inhibitory systems could give a huge contribute to many of the clinical aspects observed in patients, as epilepsy and cognitive impairment, since the excitatory/inhibitory balance is fundamental for the normal function of neural circuits. Factors outside the CNS are important in the pathogenesis of at least some aspects of the disorder, since the conditional KO model show difference in the timing of onset of some cognitive defects and in the presence of stereotypies.

show abstract

Rictor Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Suppressing Autophagy and Regulating MAPK Signaling

Cited by 18 publications

References 34 publications

E2F4 functions as a tumour suppressor in acute myeloid leukaemia via inhibition of the MAPK signalling pathway by binding to EZH2

E2F4 functions as a tumour suppressor in acute myeloid leukaemia via inhibition of the MAPK signalling pathway by binding to EZH2

Parp3 promotes astrocytic differentiation through a tight regulation of Nox4-induced ROS and mTorc2 activation

New insights into creatine transporter deficiency

Contact Info

Product

Resources

About