Methylation-sensitive Regulation of TMS1/ASC by the Ets Factor, GA-binding Protein-α

Lucas, Mary E.; Crider, Krista S.; Powell, Doris R.; Kapoor-Vazirani, Priya; Vertino, Paula M.

doi:10.1074/jbc.m901104200

Cited by 18 publications

(15 citation statements)

References 49 publications

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“…Additionally, Lucas et al showed that GABPA was selectively enriched at HS2 in human cells, and its occupancy was inversely correlated with CpG island methylation of the TMS1 gene [39]. These results suggest the epigenetic regulation of GABPA expression.…”

Section: Discussionmentioning

confidence: 99%

GABPA predicts prognosis and inhibits metastasis of hepatocellular carcinoma

Zhang

Ji³

et al. 2017

BMC Cancer

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BackgroundIncreasing evidence indicates that abnormal expression of GABPA is associated with tumor development and progression. However, the function and clinicopathological significance of GABPA in hepatocellular carcinoma (HCC) remain obscure.MethodsThe mRNA and protein expression of GABPA in HCC clinical specimens and cell lines was examined by real-time PCR and western blotting, respectively. Follow-up data were used to uncover the relationship between GABPA expression and the prognosis of HCC patients. HCC cell lines stably overexpressing or silencing GABPA were established to explore the function of GABPA in HCC cell migration and invasion by Transwell and wound healing assays in vitro and in a xenograft model in vivo. Restoration of function analysis was used to examine the underlying molecular mechanisms.ResultsGABPA was downregulated at the protein and mRNA levels in HCC tissues compared with adjacent normal tissues. Decreased GABPA expression was correlated with alpha-fetoprotein levels (P = 0.001), tumor grade (P = 0.017), and distant metastasis (P = 0.021). Kaplan-Meier survival analysis showed that patients with lower GABPA expression had significantly shorter survival times than those with higher GABPA (P = 0.031). In vivo and in vitro assays demonstrated that GABPA negatively regulated HCC cell migration and invasion, and the effect of GABPA on HCC cell migration was mediated at least partly by the regulation of E-cadherin.ConclusionsCollectively, our data indicate that GABPA inhibits HCC cell migration by modulating E-cadherin and could serve as a novel biomarker for HCC prognosis. GABPA may act as a tumor suppressor during HCC progression and metastasis, and is a potential therapeutic target in HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3373-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

GABPA predicts prognosis and inhibits metastasis of hepatocellular carcinoma

Zhang

Ji³

et al. 2017

BMC Cancer

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“…There is evidence that the activity of each of these transcription factors is affected by the presence or absence of DNA methylation (3,(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). For some of these transcription factors, the databases contained multiple identical position weight matrices.…”

Section: Methodsmentioning

confidence: 99%

Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus

Suderman

McGowan

Sasaki

et al. 2012

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

284

186

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Early life experience is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCOR-TICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, it is unlikely that such effects completely capture the evolutionarily conserved epigenetic mechanisms of early adaptation to environment. Here we present DNA methylation profiles spanning 6.5 million base pairs centered at the NR3C1 gene in the hippocampus of humans who experienced abuse as children and nonabused controls. We compare these profiles to corresponding DNA methylation profiles in rats that received differential levels of maternal care. The profiles of both species reveal hundreds of DNA methylation differences associated with early life experience distributed across the entire region in nonrandom patterns. For instance, methylation differences tend to cluster by genomic location, forming clusters covering as many as 1 million bases. Even more surprisingly, these differences seem to specifically target regulatory regions such as gene promoters, particularly those of the protocadherin α, β, and γ gene families. Beyond these high-level similarities, more detailed analyses reveal methylation differences likely stemming from the significant biological and environmental differences between species. These results provide support for an analogous cross-species epigenetic regulatory response at the level of the genomic region to early life experience.conservation | neuronal plasticity V ariation in early life experience is associated with differences in life-long health and behavioral trajectories in animals as well as humans. For example, differences in maternal care in rats during the first week of life are associated with long-term effects on behavior and brain function that persist into adulthood, including alterations in the stress response (1). In humans, similar effects are observed. For instance, childhood maltreatment associates with development of both externalizing and internalizing personality traits and psychopathology in adulthood (2). The association in both rats and humans of stable developmental phenotypes with early life experience suggests that molecular mechanisms may serve as a memory of these early life experiences in both species. In fact, there is evidence that these long-term effects are, at least in part, mediated by epigenetic alterations in the brain. In particular, recent studies have found aberrant DNA methylation in the NR3C1 (GLUCOCORTICOID RECEPTOR) gene promoter of the hippocampi of both rats and humans associated with differential early life experience (3, 4). Exposure of infant rats to stressed caretakers displaying abusive behavior produced persisting changes in methylation of the BDNF gene promoter in the adult prefrontal cortex (5). Early life stress in mice caused sustained DNA hypomethylation of an important regulatory region of the AVP gene (6).Although explanations involving a single site are appealing, it is unlikely that the broad systemic response to early life experien...

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“…The reaction protocol began with a 3 min hot start at 95°C and followed with cycles of 95°C, 10 s; 55°C, 60 s. Melt curve analysis verified a single product. Relative quantities were calculated, standardized by comparison to 18 S rRNA (small ribosomal subunit) (23). Primers used were as follows: STRAD␣ (forward-GCCAT-GTCCCCTTTAAGGAT, reverse-TCATGGTCAGCTCCT-CAGC), 18 S (forward-GAGGGAGCCTGAGAAACGG, reverse-GTCGGGAGTGGGTAATTTGC).…”

Section: Methodsmentioning

confidence: 99%

STE20-related Kinase Adaptor Protein α (STRADα) Regulates Cell Polarity and Invasion through PAK1 Signaling in LKB1-null Cells

Eggers

Kline

Zhong

et al. 2012

Journal of Biological Chemistry

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Background: STRAD␣ is the cofactor of the tumor suppressor LKB1; however, it is unclear if STRAD␣ has LKB1-independent roles. Results: STRAD␣ complexes with the kinase PAK1 to modify PAK1 phosphorylation likely via rac1 and control cell motility when LKB1 is null. Conclusion: STRAD␣ regulates PAK1 in LKB1-null cells to oversee cancer cell polarity and invasion. Significance: This shows an undiscovered role of STRAD␣ distinct from the LKB1 pathway.

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Methylation-sensitive Regulation of TMS1/ASC by the Ets Factor, GA-binding Protein-α

Cited by 18 publications

References 49 publications

GABPA predicts prognosis and inhibits metastasis of hepatocellular carcinoma

GABPA predicts prognosis and inhibits metastasis of hepatocellular carcinoma

Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus

STE20-related Kinase Adaptor Protein α (STRADα) Regulates Cell Polarity and Invasion through PAK1 Signaling in LKB1-null Cells

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