The DNA Glycosylase T:G Mismatch-specific Thymine DNA Glycosylase Represses Thyroid Transcription Factor-1-activated Transcription

Missero, Caterina; Pirro, Maria Teresa; Simeone, Silvana; Pischetola, M.; Lauro, Roberto Di

doi:10.1074/jbc.m104963200

Cited by 75 publications

(52 citation statements)

References 53 publications

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“…Screening of the library was performed essentially following instructions for the ProQuest two-hybrid system (Life Technologies) and has been previously described. 35 The GAL4 DNA-binding domain/human Akt fusion was obtained from Dr. Alfonso Bellacosa (Fox Chase Cancer Center, Philadelphia, PA, USA). Subsequently, yeast pLEx4-Akt plasmid was transformed with the pPC86AD cDNA library and plated onto plates lacking histidine in the presence of 3AT Western blotting.…”

Section: Methodsmentioning

confidence: 99%

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

Quintavalle

Incoronato²,

Puca

et al. 2010

Cell Death Differ

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Akt is a serine-threonine kinase that has an important role in transducing survival signals. Akt also regulates a number of proteins involved in the apoptotic process. To find new Akt interactors, we performed a two-hybrid screening in yeast using full-length Akt cDNA as bait and a human cDNA heart library as prey. Among 200 clones obtained, two of them were identified as coding for the c-FLIP L protein. c-FLIP L is an endogenous inhibitor of death receptor-induced apoptosis through the caspase-8 pathway. Using co-immunoprecipitation experiments of either transfected or endogenous proteins, we confirmed the interaction between Akt and c-FLIP L . Furthermore, we observed that c-FLIP L overexpression interferes with Gsk3-b phosphorylation levels. Moreover, through its effects on Gsk3b, c-FLIP L overexpression in cancer cells induced resistance to tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL). This effect was mediated by the regulation of p27 Kip1 and caspase-3 expression. These results indicate the existence of a new mechanism of resistance to TRAIL in cancer cells, and unexpected functions of c-FLIP L .

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Section: Methodsmentioning

confidence: 99%

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

Quintavalle

Incoronato²,

Puca

et al. 2010

Cell Death Differ

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“…In fact, in vitro studies have demonstrated that TDG stimulated RAR/RXR-dependent transactivation (Um et al, 1998). Furthermore, TDG has been shown to be a strong repressor of thyroid transcription factor-1 (TTF-1) transcriptional activity (Missero et al, 2001), indicating that TDG may function both as a positive and negative regulator of transcription. Whether the transcription-associated activity of TDG is modulated by sumoylation is presently not known.…”

Section: Structural Aspectsmentioning

confidence: 99%

Uracil in DNA – occurrence, consequences and repair

2002

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“…A/P endonuclease Ref-1 activates c-Jun and p53 (52,53). TDG was identified as a c-Jun-interacting protein by yeast two-hybrid screening (54) and found to repress the activity of the homeodomain-containing thyroid transcription factor-1 (55). In the present study, we have investigated the role for TDG as a coactivator for ER␣.…”

mentioning

confidence: 99%

T:G Mismatch-specific Thymine-DNA Glycosylase Potentiates Transcription of Estrogen-regulated Genes through Direct Interaction with Estrogen Receptor α

Chen

Lucey

Phoenix

et al. 2003

Journal of Biological Chemistry

112

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Nuclear receptors (NR) classically regulate gene expression by stimulating transcription upon binding to their cognate ligands. It is now well established that NR-mediated transcriptional activation requires the recruitment of coregulator complexes, which facilitate recruitment of the basal transcription machinery through direct interactions with the basal transcription machinery and/or through chromatin remodeling. However, a number of recently described NR coactivators have been implicated in cross-talk with other nuclear processes including RNA splicing and DNA repair. T:G mismatch-specific thymine DNA glycosylase (TDG) is required for base excision repair of deaminated methylcytosine. Here we show that TDG is a coactivator for estrogen receptor ␣ (ER␣). We demonstrate that TDG interacts with ER␣ in vitro and in vivo and suggest a separate role for TDG to its established role in DNA repair. We show that this involves helix 12 of ER␣. The region of interaction in TDG is mapped to a putative ␣-helical motif containing a motif distinct from but similar to the LXXLL motif that mediates interaction with NR. Together with recent reports linking TFIIH in regulating NR function, our findings provide new data to further support an important link between DNA repair proteins and nuclear receptor function.Nuclear receptors (NR) 1 regulate gene expression upon binding to small lipophilic molecules. The NR superfamily encompasses high affinity receptors for the steroid hormones, vitamin D3, thyroid hormone, and retinoic acid as well as so-called "orphan receptors" that bind with low affinity to dietary lipids such as fatty acids, oxysterols, bile acids, and xenobiotics and a large number of receptors with no known ligand (1). Two related estrogen receptors (ER␣) are responsible for the major estrogenic responses in mammals, being required for male and female reproductive function, but also for bone maintenance in the cardiovascular system and in regulating certain brain functions (2, 3).NR share a common modular structure with a core DNA binding domain and a C-terminal ligand binding domain (LBD). The LBD functions as a ligand-dependent transcription activation domain (AF2) as well as providing a surface for interaction with other NR. Transcription activation is mediated by synergism between AF2 and a second transactivation domain (AF1) located N-terminal to the DNA binding domain (4,5). Whereas AF2 activity requires ligand binding, AF1 activity is subject to regulation by phosphorylation (6 -8).Transcription regulation by NR occurs through direct interaction with the transcription machinery and/or by recruitment of coregulator proteins that facilitate interaction with the transcription machinery. Moreover, chromatin-remodeling complexes are now known to play an important role in gene transcription (9 -12). Several coactivator proteins associate with ligand-bound NR and include the p160 proteins, SRC1, TIF2/ GRIP1, and pCIP/ACTR/AIB1/RAC3/TRAM-1 (13). The thyroid hormone receptor-associated protein complex (14), which is v...

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The DNA Glycosylase T:G Mismatch-specific Thymine DNA Glycosylase Represses Thyroid Transcription Factor-1-activated Transcription

Cited by 75 publications

References 53 publications

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

Uracil in DNA – occurrence, consequences and repair

T:G Mismatch-specific Thymine-DNA Glycosylase Potentiates Transcription of Estrogen-regulated Genes through Direct Interaction with Estrogen Receptor α

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