In CEM cells the autosomal deafness gene dfna5 is regulated by glucocorticoids and forskolin

Webb, M. Scott; Miller, Aaron L.; Thompson, E. Brad

doi:10.1016/j.jsbmb.2007.02.004

Cited by 19 publications

(19 citation statements)

References 25 publications

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“…GSDME functions downstream of caspase-3 to switch apoptotic cell death to secondary necrotic/pyroptotic cell death 9,11 . To investigate whether GSDME plays additional roles in the apoptotic program, we studied its contribution to glucocorticoid-induced T-lymphoblastic leukemia cell killing 25,26 , because glucocorticoids have been shown to up-regulate GSDME messenger RNA in the human T-lymphoblastic leukemia cell line CEM-C7 27 . Treatment of CEM-C7 with the glucocorticoid triamcinolone acetonide (TA) induces upregulation and processing of GSDME (Fig.…”

Section: Resultsmentioning

confidence: 99%

Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation

et al. 2019

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Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells. GSDME deficiency also accelerates cell growth in culture and in a mouse model of melanoma. Phosphomimetic mutation of the highly conserved phosphorylatable Thr6 residue of GSDME, inhibits its pore-forming activity, thus uncovering a potential mechanism by which GSDME might be regulated. Like GSDME-N, inflammasome-generated gasdermin D-N (GSDMD-N), can also permeabilize the mitochondria linking inflammasome activation to downstream activation of the apoptosome. Collectively, our results point to a role of gasdermin proteins in targeting the mitochondria to promote cytochrome c release to augment the mitochondrial apoptotic pathway.

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Section: Resultsmentioning

confidence: 99%

Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation

et al. 2019

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“…Induction of DFNA5 mRNA correlates with glucocorticoid-dependent apoptosis of the cells. In this case, however, its expression alone was not sufficient for apoptosis induction [85]. …”

Section: Resultsmentioning

confidence: 99%

An Integrated Bioinformatics and Computational Biology Approach Identifies New BH3-Only Protein Candidates

Hawley

Chen²,

Riz³

et al. 2012

TOBIOJ

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In this study, we utilized an integrated bioinformatics and computational biology approach in search of new BH3-only proteins belonging to the BCL2 family of apoptotic regulators. The BH3 (BCL2 homology 3) domain mediates specific binding interactions among various BCL2 family members. It is composed of an amphipathic α-helical region of approximately 13 residues that has only a few amino acids that are highly conserved across all members. Using a generalized motif, we performed a genome-wide search for novel BH3-containing proteins in the NCBI Consensus Coding Sequence (CCDS) database. In addition to known pro-apoptotic BH3-only proteins, 197 proteins were recovered that satisfied the search criteria. These were categorized according to α-helical content and predictive binding to BCL-xL (encoded by BCL2L1) and MCL-1, two representative anti-apoptotic BCL2 family members, using position-specific scoring matrix models. Notably, the list is enriched for proteins associated with autophagy as well as a broad spectrum of cellular stress responses such as endoplasmic reticulum stress, oxidative stress, antiviral defense, and the DNA damage response. Several potential novel BH3-containing proteins are highlighted. In particular, the analysis strongly suggests that the apoptosis inhibitor and DNA damage response regulator, AVEN, which was originally isolated as a BCL-xL-interacting protein, is a functional BH3-only protein representing a distinct subclass of BCL2 family members.

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“…another gene with high expression in this study was DFNA5. This gene encodes proteins located in a number of organs, including the cortex of the brain and the ovaries (67)(68)(69)(70).…”

Section: Discussionmentioning

confidence: 99%

Expression of genes involved in neurogenesis, and neuronal precursor cell proliferation and development: Novel pathways of human ovarian granulosa cell differentiation and transdifferentiation capability in�vitro

et al. 2020

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In CEM cells the autosomal deafness gene dfna5 is regulated by glucocorticoids and forskolin

Cited by 19 publications

References 25 publications

Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation

Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation

An Integrated Bioinformatics and Computational Biology Approach Identifies New BH3-Only Protein Candidates

Expression of genes involved in neurogenesis, and neuronal precursor cell proliferation and development: Novel pathways of human ovarian granulosa cell differentiation and transdifferentiation capability in�vitro

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