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Fig. 7 | Stem Cell Research & Therapy

Fig. 7

From: A systematic summary of survival and death signalling during the life of hair follicle stem cells

Fig. 7

The apoptotic pathway in HFSCs. There are two apoptotic pathways, namely, the intrinsic pathway initiated by intracellular stresses (e.g., ROS and DNA damage) and the extrinsic pathway triggered by extracellular cues. a Intrinsic stressors upregulate the expression/activation of proapoptotic BCL-2 family members and suppress anti-apoptotic BCL-2 family proteins, resulting in MOMP. Intrinsic stressors can also induce the overexpression of proapoptotic proteins (e.g., NOXA (proapoptotic BH3-only protein, also known as PMAIP1 [phorbol-12-myristate-13-acetate-induced protein 1]), p53 upregulated modulator of apoptosis (PUMA), and apoptosis regulator Bcl-2-associated X protein (Bax)) in the p53-based apoptotic pathway, which is induced by the activation and stabilization of p53 through phosphorylation leading to its nuclear translocation, DNA binding and transcriptional initiation. Once MOMP is induced, cyt-c is released from the mitochondrial intermembrane and associates with caspase-9 and Apaf-1 to form apoptosomes, which can activate caspase-3 or caspase-7, causing apoptosis. b The extrinsic apoptotic pathway is triggered by the combination of the tumour necrosis factor receptor (TNFR) family members and specific TNF family ligands, leading to a caspase response. Once bound, TNFR/TNF undergoes a conformational change resulting in the recruitment of Fas-associated death domain (FADD) and subsequently pro-caspases-8 to form the death-inducing signalling complex (DISC). Finally, activated and cleaved caspase-3 leads to the occurrence of apoptosis, with characteristic changes such as phosphatidylserine plasma membrane exposure, DNA fragmentation, and the formation of apoptotic bodies. Remarkably, the intrinsic and extrinsic pathways are connected via the Bid protein. The T-shaped lines indicate inhibitory interactions involved in this pathway, and the solid arrows indicate activating interactions

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