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ER Stress As Modulator of Autophagy Pathways

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Endoplasmic Reticulum Stress in Health and Disease

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Abstract

Different physiological and pathological situations that produce alterations in the endoplasmic reticulum, lead to a condition known as ER stress homeostasis. ER stress activates a complex intracellular signal transduction pathway, called unfolded protein response (UPR). UPR is tailored essentially to re-establish ER homeostasis. However, when persistent, ER stress can switch the cytoprotective functions of UPR into cell death promoting mechanisms. One of the cellular mechanisms that are regulated by ER stress is autophagy. Autophagy is a cellular process by which different cytoplasmic components including organelles are targeted for degradation to the autophagosomes. Interestingly, like ER stress, autophagy can be a protective or a cell-death promoting mechanism. In this chapter we will review some of the mechanisms that have been proposed to participate in the regulation of autophagy by ER stress and the UPR. Likewise, we will discuss the potential therapeutic implications of the coordinated regulation of these two cellular mechanisms in cancer and cancer treatments.

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Abbreviations

ATF4:

Activating Transription Factor 4

ATF6:

Activating Transription Factor 6

Atg:

autophagy gene

Bad:

Bcl-2 antagonist of cell death

Bak:

Bcl-2 antagonist/killer

Bax:

Bcl2-Associated X Protein

Bcl-2:

B-cell lymphoma 2

BH3:

Bcl-2 Homology 3

Bim:

Bcl2-interacting mediator of cell death

BiP:

immunoglobulin heavy chain-binding protein

CHOP:

CAAT/enhancer binding protein (C/EBP) homologous protein

DAPK:

death associated protein kinase

eIF2α:

eukaryotic initiation factor-2α

ER:

endoplasmic reticulum

ERSE:

ER stress response element

GADD34:

growth arrest and DNA damage-inducible gene 34

HO-1:

heme oxygenase 1

Hsp:

heat shock protein

IP3R:

inositol 1,4,5- trisphosphate receptor

IRE1:

Iiositol requiring enzyme 1

JNK:

c-Jun N-terminal kinase

LC3:

microtubule-associated protein light chain 3

MAPK:

mitogen activated protein kinase

NF-κB:

nuclear factor κB

PERK:

RNA dependent protein kinase (PKR)-like ER kinase

PP1:

protein phosphatase 1

PP2A:

protein phosphatase 2A

Puma:

p53 upregulated mediator of apoptosis

ROS:

reactive oxygen species

SERCA:

sarco/endoplasmic reticulum Ca2+ATPase

TRAF2:

TNF (Tumor Necrosis Factor) receptor associated factor 2

TRB3:

Tribbles homologue 3

UPR:

unfolded protein response

UPRE:

UPR response element

XBP1(u/s):

X-box Binding protein 1(unspliced/spliced).

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  1. Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, C/José Antonio Nováis 2, 28040, Madrid, Spain

    María Salazar, Sonia Hernández-Tiedra, Mar Lorente & Guillermo Velasco

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  1. María Salazar
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  2. Sonia Hernández-Tiedra
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  3. Mar Lorente
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  4. Guillermo Velasco
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Correspondence to Guillermo Velasco .

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  1. Dept Molec Cell Bio, K.U. Leuven, Harestraat/Gasthuisberg, B-3000 Leuven, 3000, Belgium

    Patrizia Agostinis

  2. School of Natural Science, Department of Biochemistry, NUI Galway, University Road, Galway, Ireland

    Samali Afshin

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Salazar, M., Hernández-Tiedra, S., Lorente, M., Velasco, G. (2012). ER Stress As Modulator of Autophagy Pathways. In: Agostinis, P., Afshin, S. (eds) Endoplasmic Reticulum Stress in Health and Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4351-9_7

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