Dataset Information

LC3A and Aggresomes: A trigger for UPR-activation, mitochondrial dysfunction, and cellular senescence

ABSTRACT: The protein quality control (PQC) network is crucial for maintaining cellular proteostasis by monitoring protein production, folding, and degradation. Unfolded protein response (UPR) and autophagy are key components of this network along with the compartmentalization of misfolded proteins into inclusion bodies. Among inclusion bodies, aggresomes, a bimolecular condensate, formed by collapsed vimentin cage surrounding misfolded/aggregated proteins at the microtubule organizing center. LC3A, a member of the LC3 family of autophagy-related proteins, has been implicated in regulating protein homeostasis. In this study, we investigated the role of LC3A in aggresome-positive cells. Expression of LC3A-mediated autophagy was associated with activation of the PERK-eIF2-ATF4 axis of the UPR and alterations in mitochondrial morphology. Prolonged expression of LC3A induced cellular senescence in aggresome-positive cells. These findings provide insights into the specialized role of LC3A in cellular homeostasis. Understanding the molecular mechanisms underlying LC3A-mediated autophagy has implications for therapeutic strategies targeting protein quality control pathways.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Brain Cancer

SUBMITTER: Nada Amer

LAB HEAD: Shahenda El-Naggar

PROVIDER: PXD043703 | Pride | 2024-08-10

REPOSITORIES: Pride

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			Action	DRS
	220314_CCHE45_Myc-48hr_1.raw	Raw
	220314_CCHE45_Myc-48hr_2.raw	Raw
	220314_CCHE45_Myc-48hr_3.raw	Raw
	220314_CCHE45_Myc-96hr_1.raw	Raw
	220314_CCHE45_Myc-96hr_2.raw	Raw

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Publications

LC3A-mediated autophagy elicits PERK-eIF2α-ATF4 axis activation and mitochondrial dysfunction: Exposing vulnerability in aggresome-positive cancer cells.

Amer Nada N Hesham Dina D Al-Shehaby Nouran N Elshoky Hisham A HA Amer May M Magdeldin Sameh S Mansour Manar M Abou-Aisha Khaled K El-Naggar Shahenda S

The Journal of biological chemistry 20240520 6

The unfolded protein response pathways (UPR), autophagy, and compartmentalization of misfolded proteins into inclusion bodies are critical components of the protein quality control network. Among inclusion bodies, aggresomes are particularly intriguing due to their association with cellular survival, drug resistance, and aggresive cancer behavior. Aggresomes are molecular condensates formed when collapsed vimentin cages encircle misfolded proteins before final removal by autophagy. Yet significa ...[more]

PMID: 38777145

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