The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family

Heath-Engel, Hannah M.; Chang, Natasha C.; Shore, Gordon C.

doi:10.1038/onc.2008.309

Cited by 252 publications

(204 citation statements)

References 206 publications

(277 reference statements)

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“…Intriguingly, the so-called BAG domain, found in various proteins, including Bat3, was first identified via its interaction with Bcl-2, a TA protein (Janiak et al, 1994) implicated in the regulation of apoptosis (Heath-Engel et al, 2008). Hence, one could speculate that the modulation of apoptosis and proliferation ascribed to Bat3 (Scythe) (Desmots et al, 2005) might reflect a BAG-domain-dependent interaction with TA proteins such as Bcl-2.…”

Section: Discussionmentioning

confidence: 99%

Bat3 promotes the membrane integration of tail-anchored proteins

Leznicki

Clancy

Schwappach

et al. 2010

Journal of Cell Science

120

184

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SummaryThe membrane integration of tail-anchored proteins at the endoplasmic reticulum (ER) is post-translational, with different tail-anchored proteins exploiting distinct cytosolic factors. For example, mammalian TRC40 has a well-defined role during delivery of tail-anchored proteins to the ER. Although its Saccharomyces cerevisiae equivalent, Get3, is known to function in concert with at least four other components, Get1, Get2, Get4 and Get5 (Mdy2), the role of additional mammalian proteins during tail-anchored protein biogenesis is unclear. To this end, we analysed the cytosolic binding partners of Sec61b, a well-defined substrate of TRC40, and identified Bat3 as a previously unknown interacting partner. Depletion of Bat3 inhibits the membrane integration of Sec61b, but not of a second, TRC40-independent, tail-anchored protein, cytochrome b5. Thus, Bat3 influences the in vitro membrane integration of tail-anchored proteins using the TRC40 pathway. When expressed in Saccharomyces cerevisiae lacking a functional GET pathway for tail-anchored protein biogenesis, Bat3 associates with the resulting cytosolic pool of non-targeted chains and diverts it to the nucleus. This Bat3-mediated mislocalisation is not dependent upon Sgt2, a recently identified component of the yeast GET pathway, and we propose that Bat3 either modulates the TRC40 pathway in higher eukaryotes or provides an alternative fate for newly synthesised tail-anchored proteins.

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Section: Discussionmentioning

confidence: 99%

Bat3 promotes the membrane integration of tail-anchored proteins

Leznicki

Clancy

Schwappach

et al. 2010

Journal of Cell Science

120

184

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“…CHOP can also activate expression of proapoptotic members of BCL-2 family of genes. 47,48 Interestingly, although Perk -/-and Atf4 -/-cells and dominant negative eIF2α (Ser51Ala) knock-in cells fail to induce CHOP during ER stress, these cells are also hypersensitive to ER stress and hypoxia and display increased apoptotic potential suggesting that the PERK-ATF4 pathway acts predominatly as a prosurvival rather than prodeath pathway. 29,42,49,50 Tumors derived from these mutant cells remarkably display numerous phenotypic similarities.…”

Section: Met-trna Imentioning

confidence: 99%

Role of ATF4 in regulation of autophagy and resistance to drugs and hypoxia

Rzymski¹,

Milani²,

Singleton³

et al. 2009

Cell Cycle

171

130

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“…2,9 However, several members, including BCL-2, BAX and BAK, are also present on other organelles, most notably the endoplasmic reticulum (ER), where they have been reported to be involved in the regulation of calcium homeostasis, autophagy and ER stress responses. 2,[10][11][12][13][14][15] BOK (BCL-2-related ovarian killer) was identified in a yeast two-hybrid screen using MCL-1 as bait and was shown to selectively interact with MCL-1 and BFL-1/A1 but not with BCL-2 or BCL-X L . 16,17 Among the BCL-2 family members, BOK shows the highest evolutionary conservation.…”

mentioning

confidence: 99%

Intracellular localization of the BCL-2 family member BOK and functional implications

et al. 2013

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The pro-apoptotic BCL-2 family member BOK is widely expressed and resembles the multi-BH domain proteins BAX and BAK based on its amino acid sequence. The genomic region encoding BOK was reported to be frequently deleted in human cancer and it has therefore been hypothesized that BOK functions as a tumor suppressor. However, little is known about the molecular functions of BOK. We show that enforced expression of BOK activates the intrinsic (mitochondrial) apoptotic pathway in BAX/ BAK-proficient cells but fails to kill cells lacking both BAX and BAK or sensitize them to cytotoxic insults. Interestingly, major portions of endogenous BOK are localized to and partially inserted into the membranes of the Golgi apparatus as well as the endoplasmic reticulum (ER) and associated membranes. The C-terminal transmembrane domain of BOK thereby constitutes a 'tail-anchor' specific for targeting to the Golgi and ER. Overexpression of full-length BOK causes early fragmentation of ER and Golgi compartments. A role for BOK on the Golgi apparatus and the ER is supported by an abnormal response of Bok-deficient cells to the Golgi/ER stressor brefeldin A. Based on these results, we propose that major functions of BOK are exerted at the Golgi and ER membranes and that BOK induces apoptosis in a manner dependent on BAX and BAK.

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The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family

Cited by 252 publications

References 206 publications

Bat3 promotes the membrane integration of tail-anchored proteins

Bat3 promotes the membrane integration of tail-anchored proteins

Role of ATF4 in regulation of autophagy and resistance to drugs and hypoxia

Intracellular localization of the BCL-2 family member BOK and functional implications

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