Protein Kinase C Isozymes and Autophagy during Neurodegenerative Disease Progression

Kaleli, Hümeyra Nur; Özer, Ebru; Kaya, Veysel Oğulcan; Kutlu, Özlem

doi:10.3390/cells9030553

Cited by 27 publications

(19 citation statements)

References 222 publications

(196 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PKCε also promotes cell survival by functioning as an anti-apoptotic kinase [3,[7][8][9][10]. Recent studies implicate PKC isozymes, including PKCε, in autophagy [11,12].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells

Basu

2020

IJMS

View full text Add to dashboard Cite

Protein kinase C-ε (PKCε), an anti-apoptotic protein, plays critical roles in breast cancer development and progression. Although autophagy is an important survival mechanism, it is not known if PKCε regulates autophagy in breast cancer cells. We have shown that silencing of PKCε by siRNA inhibited basal and starvation-induced autophagy in T47D breast cancer cells as determined by the decrease in LC3-II, increase in p62, and decrease in autophagy puncta both in the presence and absence of bafilomycin A1. The mechanistic target of rapamycin (mTOR) associates with Raptor or Rictor to form complex-1 (mTORC1) or complex-2 (mTORC2), respectively. Knockdown of PKCε attenuated an increase in autophagy caused by the depletion of Raptor and Rictor. Overexpression of PKCε in MCF-7 cells caused activation of mTORC1 and an increase in LC3-I, LC3-II, and p62. The mTORC1 inhibitor rapamycin abolished the increase in LC3-I and p62. Knockdown of mTOR and Rictor or starvation enhanced autophagy in PKCε overexpressing cells. While overexpression of PKCε in MCF-7 cells inhibited apoptosis, it induced autophagy in response to tumor necrosis factor-α. However, inhibition of autophagy by Atg5 knockdown restored apoptosis in PKCε-overexpressing cells. Thus, PKCε promotes breast cancer cell survival not only by inhibiting apoptosis but also by inducing autophagy.

show abstract

“…PKCε also promotes cell survival by functioning as an anti-apoptotic kinase [3,[7][8][9][10]. Recent studies implicate PKC isozymes, including PKCε, in autophagy [11,12].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells

Basu

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…The possibility that FGFR2c could orchestrate a fine interplay between autophagy and EMT in epithelial context is also sustained by the evidence that protein kinase C isozymes, including PKCε, are also key regulators of the autophagic pathway 13 . Thus, we investigated the possible contribution of PKCε signalling on FGFR2c‐mediated repression of the autophagic process in human keratinocytes by shRNA approaches.…”

Section: Resultsmentioning

confidence: 99%

The aberrant expression in epithelial cells of the mesenchymal isoform of FGFR2 controls the negative crosstalk between EMT and autophagy

Ranieri

Guttieri

Torrisi

et al. 2021

J Cellular Molecular Medi

View full text Add to dashboard Cite

Signalling of the epithelial splicing variant of fibroblast growth factor receptor 2 (FGFR2b) triggers both differentiation and autophagy, while the aberrant expression of the mesenchymal FGFR2c isoform in epithelial cells induces impaired differentiation, inhibition of autophagy as well as the induction of the epithelial‐mesenchymal transition (EMT). In light of the widely proposed negative loop linking autophagy and EMT in the early steps of carcinogenesis, here we investigated the possible involvement of FGFR2c aberrant expression and signalling in orchestrating this crosstalk in human keratinocytes. Biochemical, molecular, quantitative immunofluorescence analysis and in vitro invasion assays, coupled to the use of specific substrate inhibitors and transient or stable silencing approaches, showed that AKT/MTOR and PKCε are the two hub signalling pathways, downstream FGFR2c, intersecting with each other in the control of both the inhibition of autophagy and the induction of EMT and invasive behaviour. These results indicate that the expression of FGFR2c, possibly resulting from FGFR2 isoform switch, could represent a key upstream event responsible for the establishment of a negative interplay between autophagy and EMT, which contributes to the assessment of a pathological oncogenic profile in epithelial cells.

show abstract

“…In the absence of nutrients and in a cellular effort to maintain the status quo, the deactivation of mTORC1 is linked to the decreased activity of ribosomal protein S6 kinase beta-1 (S6K1)/S6 protein, the elevated activation of the transcription-repressor 4E-binding protein 1, the inactivity of eukaryotic translation initiation factor 4E and, thus, the overall decreased expression of proteins. Shut-down of the growth-facilitating mTORC1 pathway, however, promotes the activity of the unc-51 like autophagy activating kinase (ULK 1/2 ) initiation complex, which launches autophagosome maturation and the cellular purging of waste products, such as Aß, Tau or α-synuclein (Huang and Manning, 2008 ; Ma and Blenis, 2009 ; Lan et al, 2017 ; Kaleli et al, 2020 ). Tuberous sclerosis (TSC) 1/2 acts as a major regulatory switch for mTORC1-mediated growth vs. autophagy and, typically in response to stressful cellular conditions and starvation, the activating phosphorylation of the cytoplasmic energy-sensor AMPK results in the AMPK-mediated phosphorylation of TSC 1/2 and the inhibition of mTORC1 (Inoki et al, 2003 ; Manning and Cantley, 2003 ; Demetriades et al, 2016 ).…”

Section: Autophagy and Mitophagymentioning

confidence: 99%

Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease

Reich

Hölscher

2020

Front. Neurosci.

View full text Add to dashboard Cite

Much thought has been given to the impact of Amyloid Beta, Tau and Alpha-Synuclein in the development of Alzheimer's disease (AD) and Parkinson's disease (PD), yet the clinical failures of the recent decades indicate that there are further pathological mechanisms at work. Indeed, besides amyloids, AD and PD are characterized by the culminative interplay of oxidative stress, mitochondrial dysfunction and hyperfission, defective autophagy and mitophagy, systemic inflammation, BBB and vascular damage, demyelination, cerebral insulin resistance, the loss of dopamine production in PD, impaired neurogenesis and, of course, widespread axonal, synaptic and neuronal degeneration that leads to cognitive and motor impediments. Interestingly, the acylated form of the hormone ghrelin has shown the potential to ameliorate the latter pathologic changes, although some studies indicate a few complications that need to be considered in the long-term administration of the hormone. As such, this review will illustrate the wide-ranging neuroprotective properties of acylated ghrelin and critically evaluate the hormone's therapeutic benefits for the treatment of AD and PD.

show abstract

Protein Kinase C Isozymes and Autophagy during Neurodegenerative Disease Progression

Cited by 27 publications

References 222 publications

Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells

Regulation of Autophagy by Protein Kinase C-ε in Breast Cancer Cells

The aberrant expression in epithelial cells of the mesenchymal isoform of FGFR2 controls the negative crosstalk between EMT and autophagy

Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease

Contact Info

Product

Resources

About