Nine-amino-acid transactivation domain: Establishment and prediction utilities

Piskacek, Simona; Gregor, Martin; Nemethova, Maria; Grábner, Martin; Kovarik, Pavel; Piskáček, Martin

doi:10.1016/j.ygeno.2007.02.003

Cited by 142 publications

(182 citation statements)

References 54 publications

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“…Bioinformatical analyses of the N-terminal sequences, predicted that there is a 9-amino-acid transactivation domain (9aa TAD) within the specific 15 N-terminal amino acids (MAVQSVLQL) of MKL1_S. 9aa TADs have been described as the smallest known denominator in the transactivation domains of a variety of transcription factors, ranging from yeast to mammals (Martin, 2009;Piskacek et al, 2007). Owing to the fact that the border between the isoform-specific parts and the shared sequence lies within this motif, the corresponding sequence in MKL1_L (SERKNVLQL) does not fulfill the criteria for such a domain (Fig.…”

Section: The Specific Mkl1_s Transcriptional Activity Requires a Novementioning

confidence: 99%

TGF-β-induced differentiation into myofibroblasts involves specific regulation of two MKL1 isoforms

Scharenberg¹,

Pippenger²,

Sack³

et al. 2014

Journal of Cell Science

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Cellular transformation into myofibroblasts is a central physiological process enabling tissue repair. Its deregulation promotes fibrosis and carcinogenesis. TGF-b is the main inducer of the contractile gene program that drives myofibroblast differentiation from various precursor cell types. Crucial regulators of this transcriptional program are serum response factor (SRF) and its cofactor MKL1 (also known as MRTF-A). However, the exact mechanism of the crosstalk between TGF-b signaling and MKL1 remains unclear. Here, we report the discovery of a novel MKL1 variant/isoform, MKL1_S, transcribed from an alternative promoter and uncover a novel translation start for the published human isoform, MKL1_L. Using a human adipose-derived mesenchymal stem cell differentiation model, we show that TGF-b specifically upregulates MKL1_S during the initial phase of myofibroblast differentiation. We identified a functional N-terminal motif in MKL1_S that allows specific induction of a group of genes including the extracellular matrix (ECM) modifiers MMP16 and SPOCK3/testican-3. We propose that TGF-b-mediated induction of MKL1_S initiates progression to later stages of differentiation towards a stationary myofibroblast.

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Section: The Specific Mkl1_s Transcriptional Activity Requires a Novementioning

confidence: 99%

TGF-β-induced differentiation into myofibroblasts involves specific regulation of two MKL1 isoforms

Scharenberg¹,

Pippenger²,

Sack³

et al. 2014

Journal of Cell Science

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“…A study in 2011 found that the TP53 proline mutation did have a profound effect on pancreatic cancer risk among males [9]. A study of Arab women found that proline homozygosity at TP53 codon (72) is associated with a decreased risk for the breast cancer [10] [11] [12]. One study suggested that TP53 codon 72 polymorphisms, p53 mutation still the most common genetic change named in human neoplasia.…”

Section: Introductionmentioning

confidence: 99%

Studying The Expression of Human P53 Gene in Patients Carrying Breast Cancer.

Edan

2017

MJS

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The gene P53 can activate DNA repair proteins when DNA has sustained damage. So, it is an important factor in aging. Also, P53 gene can also be modified by mutagens (chemicals, radiation, or viruses), increasing the likelihood for uncontrolled cell division. For this importance, we collected thirty samples from Yarmouk hospital in Baghdad, Iraq. Twenty-nine from women patients carrying breast cancer and the last one was from healthy woman, and the samples that we have taken were embedded in paraffin wax. The extracted RNA from each sample was used to check the expression of a suppressor gene (P53) via Real time PCR. We designed primers of P53 gene on encoded sequence (Exon), to make sure generation a specific PCR product of P53 gene by converting mRNA to cDNA then PCR Product. The expression of each sample was fluctuated between 0.1 fold to 0.2 fold compared with the control (the healthy sample). The highest expression showed was samples 7 (0.2 fold), and the lowest expression showed was samples 27 (0.1 fold) that compared with control expression (sample 19). While the control expression was the highest (0.25 fold) among all samples. The results indicate that tumor may affects on a suppressor gene (P53) and can decrease the gene expression, and eventually can decrease the P53 suppressor protein that can be used it in the cell protection against cancer.

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“…The site of interaction between the KIX domain and both p53-TADs corresponds with the annotated 9aaTADs and the TAF9 binding site (NMR data, eight out of nine annotated amino acids). Despite the unrecognizable sequence similarity (Table 2 and 3) 4,7 , both p53-TAD1 and p53-TAD2 share the same docking sites on the KIX domain, which may result from the presence of a common motif in the p53 transactivation domains, the 9aaTAD 8 . p53 and further well characterized 9aaTAD-transcription factors, which interact with CBP-p300 and other general co-activator GCN5 are listed in Table 3.…”

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confidence: 99%

“…None or extremely poor similarities were reported among the transactivation domains in general. Despite the enormous natural diversity, it was possible to generate a pattern and composition rules for 9aaTAD 8 . The establishment of 9aaTAD, its initial pattern and composition definition, identification and annotation (prediction correlated to experimental data) should streamline the investigations in gene regulation by transcription factors and the involvement of multiple transcriptional co-activators.…”

mentioning

confidence: 99%

“…9aaTADs interacting with CBP-p300 and other co-activators are listed: p53-9aaTADs bind to TAF9 1 and CBPp300 (KIX, TAZ1, TAZ2 and IBiD domains) 4,7 (Gal4-9aaTAD represent the 9aaTAD family) 8 , NFAT1 binds to TAF9 and CBP (TAZ-KIX and TAZ2 domains) 16 , MLL/ALL1 binds to TAF9 1 and CBP (KIX and TAZ2 domain) 2,9,17 , STAT1 binds to TAZ1 and TAZ2 domain of CBP 9 , NFkB binds to TAF9 1 and CBP 1,18 , VP16 binds to TAF9, Gal11/MED15, CBP-p300 and GCN5-PCAF 1,6,14 , EBNA2 binds to CBP-p300 (N-and C-terminal domains) and PCAF 6 , E2A binds to SAGA complex (TAF9-GCN5) and CBP (KIX domain) 19 , HSF1 binds to TAF9 1 and CBP 20 and NF-IL6 binds to TAF9 1 and p300 21 . E1A and KLF4 represent CBP-p300 binding transcription factor.…”

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confidence: 99%

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Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300

Piskáček

2009

Nature Precedings

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9aaTAD interactions with a general transcriptional co-activator TAF9/TAFII31 were reported (NMR and biochemical data: p53, VP16, HSF1, NF-IL6, NF-B and NFAT) 1 . 9aaTAD interactions with KIX domain of further general transcriptional co-activators MED15/Gal11 and CBP-p300 were recently reported (NMR data available for Oaf1, Pdr1 and p53) 2-6 . Oaf1-9aaTAD and Pdr1-9aaTAD 3 upon binding to KIX domain of Med15/Gal11 (9 resp. 12 amino acid long peptides including 9aaTAD) reveal structural similarity, although none of the nine amino acids is conserved in both 9aaTADs (Table 1).The interaction between TAF9 and p53-TAD1 was restricted by NMR to five amino acids (FSDLW) in the first annotated 9aaTAD of p53 (p53-9aaTAD1). The second annotated 9aaTAD (p53-9aaTAD2) and the pseudo-9aaTAD (p53-9aaTADpse) were located in p53-TAD2 (annotated results from 2007 available on www.expasy.ch/tools). Both p53-9aaTAD1 and p53-9aaTAD2 fulfil the criteria of 9aaTAD pattern, amino acid composition and hydrophobic profile (Fig.1).

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Nine-amino-acid transactivation domain: Establishment and prediction utilities

Cited by 142 publications

References 54 publications

TGF-β-induced differentiation into myofibroblasts involves specific regulation of two MKL1 isoforms

TGF-β-induced differentiation into myofibroblasts involves specific regulation of two MKL1 isoforms

Studying The Expression of Human P53 Gene in Patients Carrying Breast Cancer.

Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300

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