PLIC proteins or ubiquilins regulate autophagy‐dependent cell survival during nutrient starvation

N’Diaye, Elsa-Noah; Kajihara, Kimberly K.; Hsieh, Ivy; Morisaki, Hiroshi; Debnath, Jayanta; Brown, Eric J.

doi:10.1038/embor.2008.238

Cited by 287 publications

(304 citation statements)

References 34 publications

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“…Furthermore, increased LC3 conversion into LC3-II was seen upon autophagy inhibition with H C /ATPase inhibitor baflomycin A1. 23,24 Finally, electron microscopy confirmed the increase in autophagic vacuoles in EcdCRas overexpressing hMECs (Fig. S4B).…”

Section: Discussionsupporting

confidence: 54%

“…23 As expected, Ras-overexpressing cells showed increased levels of LC3 at various time points. Notably, while Ecd overexpression by itself had no obvious impact on LC3 levels, EcdCRas-overexpressing cells exhibited much higher levels of LC3 I and LC3 II basally (0 time point), as well as throughout the course of autophagy induction (Figs.…”

Section: Ecd Plus Ras Overexpression Induces Upregulation Of Autophagmentioning

confidence: 68%

“…LC3 may accumulate in cells through stabilization of protein due to reduced lysosomal turnover or by upregulation of transcription. 20,[22][23][24][25][26] Recent reports suggest that LC3 is transcriptionally regulated by the activation of pathways downstream of Ras. 41,42 We observed significantly higher levels of LC3B mRNA expression, suggesting a possible role of Ecd plus Ras to upregulate basal autophagy.…”

Section: Discussionmentioning

confidence: 99%

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The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells

et al. 2015

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Section: Discussionsupporting

confidence: 54%

Section: Ecd Plus Ras Overexpression Induces Upregulation Of Autophagmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells

et al. 2015

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“…Recently, Ubqln has been shown to play a role in a variety of other cellular processes, including autophagy, ER-associated protein degradation (ERAD) and receptor trafficking, presumably by regulating the abundance of proteins implicated in these events (21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Furthermore, UBQLN is one member of a family of at least five proteins (UBQLN1, UBQLN2, UBQLN3, UBQLN4, and UBQLNL) that share a high degree of similarity at the level of both amino acid and domain structure.…”

mentioning

confidence: 99%

Ubiquitination, localization, and stability of an anti-apoptotic BCL2-like protein, BCL2L10/BCLb, are regulated by Ubiquilin1

Beverly

Lockwood

Shah

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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We have previously shown that all six members of the anti-apoptotic BCL2 gene family can cooperate with (myelocytomatosis oncogene) MYC in a mouse model of leukemia, but three of them are significantly less potent contributors to leukemogenicity than the other three. The protein encoded by one of these less potent genes, BCL2L10∕BCLb, was recently shown to vary dramatically in many primary human cancers by immunohistochemistry, and the protein levels were inversely correlated with survival in patients with several cancer types. We examined BCLb mRNA in a panel of human cancer cell lines and did not observe the extensive variation in mRNA that would be required to explain the vast differences in protein levels. We found that the levels of BCLb protein diminish quickly after inhibition of protein synthesis with cycloheximide, so we searched for interacting proteins that might affect posttranslational stability of BCLb. Using a variety of approaches, including immunoaffinity and mass spectrometry, we identified a protein, Ubiquilin1 (Ubqln), that specifically interacts with BCLb, and not with other anti-apoptotic BCL2-like proteins. Ubqln stabilizes BCLb protein, while also promoting monoubiquitination on multiple lysine residues and relocation to the cytosol. Furthermore, primary lung adencarcinomas have more Ubqln mRNA than normal adjacent lung tissue, and higher Ubqln mRNA levels are associated with shorter survival of lung cancer patients, suggesting that potentiation of the anti-apoptotic potential of BCLb through regulation of its stability by Ubqln may be an important factor in tumor progression.

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“…For EGR1 knockdown, human SMARTpool EGR1 siRNA (Dharmacon, M-006526–01-0005) was used. pBABE-puro-mCherry-EFGP-LC3B was a gift from Jayanta Debnath (Addgene, 22,418) [53]. To increase the intensity of the fluorescence, the EEF1A1/EF1α promoter was cloned into the construct using NaeI restriction sites.…”

Section: Methodsmentioning

confidence: 99%

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

et al. 2018

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Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway critical for maintaining cellular homeostasis and viability, and is predominantly regarded as a rapid and dynamic cytoplasmic process. To increase our understanding of the transcriptional and epigenetic events associated with autophagy, we performed extensive genome-wide transcriptomic and epigenomic profiling after nutrient deprivation in human autophagy-proficient and autophagy-deficient cells. We observed that nutrient deprivation leads to the transcriptional induction of numerous autophagy-associated genes. These transcriptional changes are reflected at the epigenetic level (H3K4me3, H3K27ac, and H3K56ac) and are independent of autophagic flux. As a proof of principle that this resource can be used to identify novel autophagy regulators, we followed up on one identified target: EGR1 (early growth response 1), which indeed appears to be a central transcriptional regulator of autophagy by affecting autophagy-associated gene expression and autophagic flux. Taken together, these data stress the relevance of transcriptional and epigenetic regulation of autophagy and can be used as a resource to identify (novel) factors involved in autophagy regulation.

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PLIC proteins or ubiquilins regulate autophagy‐dependent cell survival during nutrient starvation

Cited by 287 publications

References 34 publications

The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells

The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells

Ubiquitination, localization, and stability of an anti-apoptotic BCL2-like protein, BCL2L10/BCLb, are regulated by Ubiquilin1

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

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