Chaperone-mediated autophagy targeting chimeras (CMATAC) for the degradation of ERα in breast cancer

Zhang, Jun; Huang, Yehong; Liu, Wenzhuo; Li, Lulu; Chen, Liming

doi:10.32604/biocell.2020.011642

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…16 The administration of urocortin, an endogenous cardiac peptide, inhibits Beclin-1-mediated autophagic cell death in cardiomyocytes in ischaemia/reperfusion injury, and the inhibition of autophagy related proteins can reduce renal tubular epithelial cell death in IRI. 17 Although autophagic cell damage is assumed to be the basis of IRI, it remains controversial whether high autophagy reduces or aggravates IRI. 3,18 It is believed that low autophagy can represent a homeostatic cellular mechanism for the turnover of organelles and proteins, but under conditions of nutrient and energy deficiency such as hypoxia or starvation, an increase in autophagy can induce cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Autophagy activated in severe ischaemia and hypoxia can aggravate brain injury and lead to autophagic cell death 16 . The administration of urocortin, an endogenous cardiac peptide, inhibits Beclin‐1‐mediated autophagic cell death in cardiomyocytes in ischaemia/reperfusion injury, and the inhibition of autophagy related proteins can reduce renal tubular epithelial cell death in IRI 17 . Although autophagic cell damage is assumed to be the basis of IRI, it remains controversial whether high autophagy reduces or aggravates IRI 3,18 .…”

Section: Discussionmentioning

confidence: 99%

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High‐altitude hypoxia‐induced rat alveolar cell injury by increasing autophagy

Zhao¹,

Hou

Tang³

et al. 2022

Int J Experimental Path

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The lung is an open system continuously exposed to external environment through the respiratory tract and is highly susceptible to environmental insults. There is considerable evidence that exposure to high-altitude hypoxia may result in a variety of cardiopulmonary diseases, posing a serious threat to human health and even life. Individuals exposed to high-altitude hypoxia may present with severe lung tissue damage and impaired

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High‐altitude hypoxia‐induced rat alveolar cell injury by increasing autophagy

Zhao¹,

Hou

Tang³

et al. 2022

Int J Experimental Path

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“…CMATAC peptides also contain three components: a membrane-penetrating peptide (TAT) that enables the peptide to pass through the plasma membrane, an αI peptide as a protein-binding peptide that specifically binds ERα, and a CMA-targeting peptide (CTM) that targets chaperon-mediated autophagy. Besides, research achieved the CMATAC-mediated targeted degradation of ERα in vitro . CMATAC based on the CMA mechanism has shown great research prospects in the treatment of HD and PD.…”

Section: Targeted Protein Degradation For Neurodegenerative Disease T...mentioning

confidence: 99%

“…Besides, research achieved the CMATACmediated targeted degradation of ERα in vitro. 144 CMATAC based on the CMA mechanism has shown great research prospects in the treatment of HD and PD. In 2021, metformin was identified as a novel inducer of CMA, demonstrating that metformin-induced activation of CMA via Hsc70 overexpression in the hippocampus of APP/PS1 mice alleviated the cognitive deficits seen in this mouse model of AD, suggesting that CMA activation has the potential to treat AD.…”

Section: Autacs For Parkinson's Diseasementioning

confidence: 99%

Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy

et al. 2022

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Neurodegenerative diseases (NDs) are currently incurable diseases that cause progressive degeneration of nerve cells. Many of the disease-causing proteins of NDs are “undruggable” for traditional small-molecule inhibitors (SMIs). None of the compounds that attenuated the amyloid-β (Aβ) accumulation process have entered clinical practice, and many phase III clinical trials of SMIs for Alzheimer’s disease (AD) have failed. In recent years, emerging targeted protein degradation (TPD) technologies such as proteolysis-targeting chimeras (PROTACs), lysosome-targeting chimaeras (LYTACs), and autophagy-targeting chimeras (AUTACs) with TPD-assistive technologies such as click-formed proteolysis-targeting chimeras (CLIPTACs) and deubiquitinase-targeting chimera (DUBTAC) have developed rapidly. In vitro and in vivo experiments have also confirmed that TPD technology can target the degradation of ND pathogenic proteins, bringing hope for the treatment of NDs. Herein, we review the latest TPD technologies, introduce their targets and technical characteristics, and discuss the emerging TPD technologies with potential in ND research, with the hope of providing a new perspective for the development of TPD technology in the NDs field.

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“…Autophagy is a lysosome-dependent cellular catabolic process by which cytoplasmic components are isolated from the rest of the cell within double-membraned structures known as autophagosomes, which subsequently fuse with lysosomes for the degradation (Mostowy, 2013). Autophagy often occurs at a low level to maintain cellular homeostasis under physiological conditions but could accelerate in response to harmful stimuli such as oxygen deprivation (Zhang et al, 2020). However, it is important to note that hypoxia-induced autophagy differs substantially across cellular contexts, as it may promote cell survival under mild hypoxic conditions but apoptosis under severe hypoxic conditions (Mazure and Pouysségur, 2010).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia induced apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway

WANG¹,

Xue²,

Zhao³

et al. 2022

Biocell

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The pathogenesis of high altitude-related gastric mucosal injury remains poorly understood, this study aimed to investigate the role of autophagy in hypoxia-induced apoptosis of rat gastric mucosal cells. Rats were randomized into four groups which were maintained at an altitude of 400 m (P) or received no treatment (H), autophagy inducer rapamycin (H+AI) or autophagy inhibitor 3-MA (H+AB) at an altitude of 4,300 m for 1, 7, 14 and 21 days, respectively, and the morphology, ultrastructure, autophagy, and apoptosis of gastric mucosal tissues were examined. Gastric mucosal epithelial cells CC-R039 were cultured under conditions of normoxia, 2% O 2 (hypoxia), or 2% O 2 +anti-mTORC1 for 0, 24, 48, and 72 h, respectively, and the autophagy and apoptosis were analyzed. CC-R039 cells were transfected with siHIF-1α, siTERT, or siRNA and the autophagy was examined. The results showed that the exposure to hypoxia increased the autophagy and apoptosis of gastric mucosal cells in rats, and apoptosis was aggravated by rapamycin treatment but alleviated by 3-MA treatment. Increased duration of hypoxia from 0 to 72 h could increase the autophagy and apoptosis but decrease the proliferation of gastric mucosal cells. Inhibition of mTORC1 with rapamycin led to further increase in apoptosis and even substantial cell death, and inhibition of HIF-1α and TERT increased mTORC1 expression and reduced autophagy. Moreover, the inhibition of HIF-1α reduced TERT expression. In conclusion, hypoxia could induce apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway. Abbreviations 3-MA:3-methyladenine HIF-1α:Hypoxia-inducible factor 1α LC3-II:Microtubule-associated protein light chain 3-II mTORC1: Mammalian target of rapamycin complex 1 TERT:Telomerase reverse transcriptase

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Chaperone-mediated autophagy targeting chimeras (CMATAC) for the degradation of ERα in breast cancer

Cited by 6 publications

References 11 publications

High‐altitude hypoxia‐induced rat alveolar cell injury by increasing autophagy

High‐altitude hypoxia‐induced rat alveolar cell injury by increasing autophagy

Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy

Hypoxia induced apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway

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