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TTC33-associated network (TAN) is a novel vertebrate-specific complex formed by TTC33, WDR61 and PHF5A

ABSTRACT: TTC33-associated network (TAN) is a novel vertebrate-specific complex formed by TTC33, WDR61 and PHF5A

PROVIDER: PRJNA980559 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24834967_1.fastq.gz	Fastqsanger.gz
	SRR24834967_2.fastq.gz	Fastqsanger.gz
	SRR24834968_1.fastq.gz	Fastqsanger.gz
	SRR24834968_2.fastq.gz	Fastqsanger.gz
	SRR24834969_1.fastq.gz	Fastqsanger.gz

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TTC33-associated network (TAN) is a novel vertebrate-specific complex formed by TTC33, WDR61 and PHF5A

Project description:TTC33 is an uncharacterized vertebrate-specific structural protein composed of tetratricopeptide repeat motifs. TTC3 forms a trimeric complex with WDR61 and chromatin binding PHF5A, coined TAN for TTC33-associated network. The TAN complex is associated with structural protein CCDC97, SF3A/B U2 splicing factor sub-complex, PP2A phosphatase and UNG DNA glycosylase.

2024-11-05 | GSE234217 | GEO

TTC33 forms a complex with WDR61 and PHF5A to recruit factors relevant to genomic integrity 2/2

Project description:The functions of many human proteins remain unknown, highlighting major gaps in our understanding of cellular biology. TTC33 is an evolutionarily conserved tetratricopeptide repeat (TPR) protein expressed across human tissues, whose molecular role is not defined. Here we identify the TTC33 partners using comparative label-free mass spectrometry. The TTC33-associated network (TAN) comprises WDR61, CCDC97, UNG1/2, PP2A-B55α, PHF5A, and components of the U2 spliceosomal complex. Using a combination of biochemical assays, structural modeling and molecular dynamics we show that TTC33 directly recruits WDR61 and PHF5A to assemble into a trimeric core complex (TANC), which then forms distinct interactions with either UNG1/2 or SF3B–CCDC97. Somatic TTC33 mutations at key TANC interface residues reduce complex stability and weaken the interaction network. We further show that WDR61 stabilizes TTC33 by protecting it from proteolytic degradation. Loss of network components induces genomic instability and activates DNA damage markers, including γH2AX and p53 phosphorylation.

2026-07-13 | PXD043138 | Pride

TTC33 forms a complex with WDR61 and PHF5A to recruit factors relevant to genomic integrity 1/2

2026-07-09 | PXD043098 | Pride

Comparative mass spectrometry reveals a novel TTC33-associated network core (TANC) complex with functions in DNA damage response

Project description:TTC33 is a 30 kDa human uncharacterized tetratricopeptide repeat protein. Here, we employed label-free mass spectrometry analysis to identify the proteins interactors. The TTC33-associated network (TAN) is composed of WDR61, PHF5A, which together with TTC33 form a trimeric core complex (TANC), that recruits UNG1/2 DNA glycosylase, uncharacterized CCDC97, SF3B, a sub-complex of U2-splicing factor, and PP2A phosphatase (PPP2R1A, PPP2CA/CB and PPP2R2A).

2026-07-06 | PXD059336 | Pride

Comparative mass spectrometry reveals a novel TTC33-associated network core (TANC) complex with functions in DNA damage response

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Comparative mass spectrometry reveals a novel TTC33-associated network core (TANC) complex with functions in DNA damage response

2026-07-06 | PXD059337 | Pride

Transcriptome-wide identification of transcripts regulated by PHF5A in colorectal cancer cells

Project description:Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here we demonstrated that PHF5A, a component of U2 snRNPs, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS, and established PHF5A as potential therapeutic target.

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PHF5A coordinates p300 for epigenetic regulation of lipogenesis to promote hepatocellular carcinoma progression

Project description:PHD-finger protein 5A (PHF5A) is a component of U2snRNP, which plays a critical role in mRNA splicing for recognizing the branch site. However, whether it also plays other functions independent of RNA splicing remains elusive. Here, we find that expression levels of PHF5A are significantly upregulated in hepatocellular carcinoma (HCC). Down-regulation of PHF5A restrains liver cancer cell proliferation in vitro and in vivo. RNA-sequencing analysis reveals that fatty-acid biosynthetic enzymes are major downstream targets of PHF5A in HCC. Through metabolomics analysis, we find that inhibition of PHF5A reduces free fatty acid and phospholipid synthesis, further suppressing plasma membrane function. Mechanistically, PHF5A acts as a transcription co-factor of the p300 acetyltransferase for the H3K27 acetylation (Ac) and promotes H3K27Ac-dependent lipogenic genes expression. Our findings demonstrated a surprising splicing-independent role of PHF5A in transcriptional regulation of lipid metabolism for HCC progression and provided a new strategy for HCC therapy by blocking the interaction of PHF5A and p300.

2021-10-01 | GSE167023 | GEO

Transcriptome analysis reveals the molecular regulatory network of dietary supplementation with succinate on muscle fiber characteristics and meat quality in Tan sheep

Project description:To investigate the impact of adding succinate to the diet on the production performance, meat quality, muscle fiber characteristics, and transcriptome of the longissimus dorsi muscle in Tan sheep, 36 Tan sheep were selected and fed with different levels of succinate (0%, 0.5%, 1.0%, 2.0%) for a 60-day trial period. Overall, compared to the control group, the addition of succinate to the diet improved the production performance, slaughter performance, and meat quality of Tan sheep. It significantly increased dry matter intake, carcass weight, eye muscle area, and the GR value while significantly reducing the shear force and cooking loss of the longissimus dorsi muscle (p<0.05). Furthermore, the addition of succinate to the diet altered the muscle fiber characteristics of the longissimus dorsi muscle in Tan sheep, significantly increasing the fiber diameter and cross-sectional area of type I and type IIa muscle fibers (p<0.05). The addition of 1.0% succinate to the diet altered the transcriptome of the longissimus dorsi muscle in Tan sheep, with 741 differentially expressed genes identified compared to the control group. These differentially expressed genes were involved in various pathways related to lipid metabolism, energy metabolism, and muscle development, such as insulin secretion, insulin resistance, cAMP signaling pathway, PI3K-Akt signaling pathway, and FoxO signaling, among others. In summary, succinate plays a crucial role in regulating energy metabolism, protein deposition, and glucose and lipid metabolism homeostasis in Tan sheep through insulin signaling pathways and the interaction of muscle cell factors. By modulating the expression of relevant genes, succinate improves the muscle fiber characteristics of Tan sheep, thereby enhancing production performance and meat quality.

2023-11-26 | GSE248353 | GEO

Nascent transript profiling upon in mouse embryonic stem cells under control conditions or Phf5a knockdown

Project description:Phf5a regulates transcription elongation in mouse embryonic stem cells (ESCs), through regulation of the Paf1 complex. In this study we assayed nascent RNA profiling using global run-on sequncing in mouse ESCs under conditions of self-renewal, differentiation and Phf5a knockdown. These results revealed that genes positively regulated by Paf1 in ESCs exibit RNA elongation pausing on their promoters. We used conditions of self-renewal, differentiation, Phf5a knockdown and Paf1 knockdown to monitor nascent transcript expression changes during Phf5a depletion using global run-on RNA sequencing (GRO-seq). These results revealed that Phf5a through the control of Paf1 complex regulates pause release and elongation of pluripoency-associated genes in embryonic stem cells.

2016-08-31 | GSE73441 | GEO

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