TFE3, HSP47, and CREB3 Pathways of the Mammalian Golgi Stress Response

Taniguchi, Masaru; Yoshida, Hiderou

doi:10.1247/csf.16023

Cited by 86 publications

(81 citation statements)

References 49 publications

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“…Recently, certain stresses that disrupt the Golgi structures and functions were defined as Golgi stress [16,17], although this concept is still ambiguous in comparison with ER stress, and the whole picture has not yet been clarified. Following treatment with Nigr, which is often used to trigger Golgi stress [18], the full-length CREB3 protein was depleted, but levels of the cleaved form of CREB3 were negligible in HEK293 cells.…”

Section: Resultsmentioning

confidence: 99%

“…In this study, we tested eight reagents to monitor endogenous CREB3 cleavage and found that BFA and Mone induced CREB3 processing in a time-dependent manner. Among members of the CREB3/ATF6 family, CREB3 activation occurs in response to Golgi stress; however, the concept and machinery of Golgi stress [16,17,27] are still obscure in comparison with those of ER stress. In particular, it is unclear whether Golgi stress is a common target of BFA and Mone (a sodium ionophore) since their pharmacological actions are not identical.…”

Section: Resultsmentioning

confidence: 99%

“…Considering these findings, canonical ER stress pathways and noncanonical ER-resident CREB3 family members are activated by distinct cellular dysfunctions, as observed in this study, but their downstream targets might partially overlap. Recently, microarray analysis using cells treated with putative Golgi stress-inducing reagents revealed a variety of candidate genes associated with protein transport, glycosylation and Golgi homeostasis [16,17,27,34]. Therefore, an elaborate comparative analysis of their promoter sequences might uncover the conserved sequences specifically recognized by members of the CREB3 family and clarify the whole picture of the Golgi stress response.…”

Section: Resultsmentioning

confidence: 99%

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Regulation of the ER‐bound transcription factor Luman/CREB3 in HEK293 cells

2019

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CREB3 is a transcription factor localized to the ER. Here, we investigated endogenous CREB3 expression in HEK293 cells using pharmacological and genome editing approaches. Full‐length CREB3 detected under resting conditions disappeared following treatment with tunicamycin, brefeldin A and nigericin. Treatment with cycloheximide and MG132 indicated that endogenous CREB3 is a proteasome substrate. Using cells deficient for the ER‐associated protein degradation (ERAD) factors SEL1L and Herp, we demonstrate that SEL1L, but not Herp, plays a crucial role in the posttranslational regulation of full‐length CREB3 expression. In addition, kifunensine, an α‐mannosidase inhibitor, remarkably increased full‐length CREB3 expression. Our study suggests that endogenous full‐length CREB3 is a novel substrate for ERAD and identifies unique cellular signals distinct from those in canonical ER stress.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Regulation of the ER‐bound transcription factor Luman/CREB3 in HEK293 cells

2019

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“…In addition to these secretory and polarity functions, the Golgi has emerged as a versatile platform that supports a broad range of cellular processes. The Golgi can actively modulate the microtubule network [19,20], forms a hub for a variety of signaling pathways [21–24] and participates in the regulation of calcium and pH homeostasis [25], stress response [26,27], apoptosis [28] and autophagy [29,30**]. …”

Section: Structure and Function Of The Golgi Apparatusmentioning

confidence: 99%

Golgi ribbon disassembly during mitosis, differentiation and disease progression

Wei

Seemann

2017

Current Opinion in Cell Biology

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The Golgi apparatus is tightly integrated into the cellular system where it plays essential roles required for a variety of cellular processes. Its vital functions include not only processing and sorting of proteins and lipids, but also serving as a signaling hub and a microtubule-organizing center. Golgi stacks in mammalian cells are interconnected into a compact ribbon in the perinuclear region. However, the ribbon can undergo distinct disassembly processes that reflect the cellular state or environmental demands and stress. For instance, its most dramatic change takes place in mitosis when the ribbon is efficiently disassembled into vesicles through a combination of ribbon unlinking, cisternal unstacking and vesiculation. Furthermore, the ribbon can also be detached and positioned at specific cellular locations to gain additional functionalities during differentiation, or fragmented to different degrees along disease progression or upon cell death. Here, we describe the major morphological alterations of Golgi ribbon disassembly under physiological and pathological conditions and discuss the underlying mechanisms that drive these changes.

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“…Like the ER, the Golgi can be stressed under prolonged anti‐HIV drug use and initiates Golgi stress response, which involves a few regulating factors/pathways: TFE3, CREB3‐ARF4 pathway, and HSP47. ( 19,20 ) TFE3 regulates transcriptional activation of genes encoding vesicular trafficking components or Golgi resident enzymes. The CREB3‐ARF4 pathway involves both ER and Golgi, in which ARF4 is a member of the small GTPase family that regulates Golgi‐to‐ER vesicular trafficking.…”

mentioning

confidence: 99%

Ritonavir and Lopinavir Suppress RCE1 and CAAX Rab Proteins Sensitizing the Liver to Organelle Stress and Injury

Khalatbari¹,

Mishra²,

Han³

et al. 2020

Hepatol Commun

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Organelle stress and Liver injuries often occur in human immunodeficiency virus (HIV) infected patients underanti-HIV therapies, yet few molecular off-targets of anti-HIV drugs have been identified in the liver. Here, we found through total RNA sequencing that the transcription of a host protease Ras converting CAAX endopeptidase 1 (RCE1) was altered in HepG2 cells treated with anti-HIV protease inhibitors, ritonavir and lopinavir. Levels of RCE1 protein were inhibited in HepG2 and primary mouse hepatocytes and in the liver of mice treated with the anti-HIV drugs, which were accompanied with inhibition of two potential substrates of RCE1, small GTP binding protein Rab13 and Rab18, which are with a common CAAX motif and known to regulate the ER-Golgi traffic or lipogenesis. Neither Rce1 transcription nor RCE1 protein level was inhibited by Brefeldin A, which is known to interfere with the ER-Golgi traffic causing Golgi stress. Knocking down Rce1 with RNA interference increased ritonavir and lopinavir-induced cell death as well as expression of Golgi stress response markers, TFE3, HSP47 and GCP60, in both primary mouse hepatocytes and mouse liver, and deteriorated alcohol-induced alanine aminotransferase (ALT) and fatty liver injury in mice. In addition, overexpressing Rab13 or Rab18 in primary human hepatocytes reduced partially the anti-HIV drugs and alcohol-induced Golgi fragmentation, Golgi stress response, and cell death injury. Conclusion: We identified a mechanism linking a host protease and its substrates, small guanosine triphosphate-binding proteins, to the anti-HIV drug-induced Golgi dysfunction, organelle stress response, and fatty liver injury. (Hepatology Communications 2020;4:932-944).

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TFE3, HSP47, and CREB3 Pathways of the Mammalian Golgi Stress Response

Cited by 86 publications

References 49 publications

Regulation of the ER‐bound transcription factor Luman/CREB3 in HEK293 cells

Regulation of the ER‐bound transcription factor Luman/CREB3 in HEK293 cells

Golgi ribbon disassembly during mitosis, differentiation and disease progression

Ritonavir and Lopinavir Suppress RCE1 and CAAX Rab Proteins Sensitizing the Liver to Organelle Stress and Injury

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