Sub1/PC4, a multifaceted factor: from transcription to genome stability

Garavís, Miguel; Calvo, Olga

doi:10.1007/s00294-017-0715-6

Cited by 29 publications

(23 citation statements)

References 154 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given the important role of PC4 in transcription regulation [19], we subsequently examined whether PC4 could directly activate c-Myc transcription to promote its expression. To confirm the relationship between PC4 and c-Myc, we performed a bioinformatic analysis for the presence of putative PC4-binding sites (BS) in the C-MYC promoter, and found two putative PC4 BS in a region encompassing 0.1 kb upstream the transcription start site (TSS).…”

Section: Resultsmentioning

confidence: 99%

Transcriptional positive cofactor 4 promotes breast cancer proliferation and metastasis through c-Myc mediated Warburg effect

et al. 2019

View full text Add to dashboard Cite

Background The human positive cofactor 4 (PC4) is initially identified as a transcriptional cofactor and has an important role in embryonic development and malignant transformation. However, the clinical significance and the molecular mechanisms of PC4 in breast cancer development and progression are still unknown. Methods We investigated PC4 expression in 114 cases of primary breast cancer and matched normal breast tissue specimens, and studied the impact of PC4 expression as well as the molecular mechanisms of this altered expression on breast cancer growth and metastasis both in vitro and in vivo. Results PC4 was significantly upregulated in breast cancer and high PC4 expression was positively correlated with metastasis and poor prognosis of patients. Gene set enrichment analysis (GSEA) demonstrated that the gene sets of cell proliferation and Epithelial-Mesenchymal Transition (EMT) were positively correlated with elevated PC4 expression. Consistently, loss of PC4 markedly inhibited the growth and metastasis of breast cancer both in vitro and in vivo. Mechanistically, PC4 exerted its oncogenic functions by directly binding to c-Myc promoters and inducing Warburg effect. Conclusions Our study reveals for the first time that PC4 promotes breast cancer progression by directly regulating c-Myc transcription to promote Warburg effect, implying a novel therapeutic target for breast cancer. Electronic supplementary material The online version of this article (10.1186/s12964-019-0348-0) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

Transcriptional positive cofactor 4 promotes breast cancer proliferation and metastasis through c-Myc mediated Warburg effect

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The human positive cofactor 4 (PC4) or Sub1 in yeast has recently attracted great attention of researchers worldwide (F. Liao et al, 2020; Mondal et al, 2019; Sikder et al, 2019). PC4 has been considered as an evolutionarily conserved transcriptional co‐activator since the first identification (Ge & Roeder, 1994), which is involved in transcriptional activation (Calvo, 2018), oxidative stress (Yu et al, 2016) histone modification (Sikder et al, 2019), and maintaining genomic stability (Garavis & Calvo, 2017). In this study, for the first time, we find that PC4 is increased and becomes activated with age, and transgenic expression of PC4 disturbs mTOR‐regulated proteostasis and causes global accelerated ageing by promoting histone acetylation.…”

Section: Introductionmentioning

confidence: 99%

Acceleration of ageing via disturbing mTOR‐regulated proteostasis by a new ageing‐associated gene PC4

Chen

Liao

et al. 2021

Aging Cell

View full text Add to dashboard Cite

Research on ageing‐associated genes is important for investigating ageing and anti‐ageing strategies. Here, we firstly reported that the human positive cofactor 4 (PC4), a multifunctional and highly conserved nucleoprotein, is accumulated and activated during ageing and causes global accelerated ageing process by disrupting proteostasis. Mechanistically, PC4 interacts with Sin3‐HDAC complex and inhibits its deacetylated activity, leads to hyper‐acetylation of the histones at the promoters of mTOR‐related genes and causes mTOR signalling activation. Accordingly, mTOR activation causes excessive protein synthesis, resulting in impaired proteostasis and accelerated senescence. These results reveal a new biological function of PC4 in vivo, recognizes PC4 as a new ageing‐associated gene and provides a genetically engineered mouse model to simulate natural ageing. More importantly, our findings also indicate that PC4 is involved in histone acetylation and serves as a potential target to improve proteostasis and delay ageing.

show abstract

“…Sub1, a conserved factor (yeast homolog of mammalian PC4) was previously found to facilitate Pol II transcription in a variety of ways 70, 71 , to be recruited to the PIC 72 , and to alter accessibility of promoter single-stranded DNA, consistent with initiation functions 73 . sub1 Δ has extensive genetic interactions with initiation factors and itself causes TSSs to shift downstream 29, 38, 50, 74 , We found sub1 Δ to confer a His + phenotype for the imd2Δ::HIS3 initiation reporter 41 and furthermore found that Pol II GOF alleles appeared epistatic to sub1 Δ, leading to the proposal that sub1 Δ effects in initiation were distinct from TFIIB or TFIIF alleles 39 .…”

Section: Resultsmentioning

confidence: 99%

Ssl2/TFIIH function in Transcription Start Site Scanning by RNA Polymerase II in Saccharomyces cerevisiae

Zhao

Vvedenskaya

Lai

et al. 2021

Preprint

View full text Add to dashboard Cite

Ssl2, as an essential subunit of the RNA Polymerase II (Pol II) general transcription factor TFIIH, promotes melting of promoter DNA through its ATPase-dependent DNA translocase activity within the Pol II pre-initiation complex. In Saccharomyces cerevisiae, after DNA melting, Ssl2 is proposed to drive Pol II scanning downstream for usable transcription start sites (TSSs) through this same ATP-dependent DNA translocase activity. However, how Pol II catalytic activity or activities of other general transcription factors integrate with Ssl2/TFIIH activity for promoter scanning and what ways Ssl2 modulates TSS selection by scanning have not been well studied. Here, we report the identification of ssl2 alleles conferring phenotypes in vivo consistent with altered Pol II initiation. We find that these ssl2 alleles alter TSS selection by scanning in ways that are distinct from how changes to Pol II or other GTF activities alter TSS selection by scanning. Specific predictions arise for interactions among initiation mutants depending on whether they function in promoter scanning through modulating initiation at an individual TSS or if they control the probability that a TSS is reached during the scanning process (scanning processivity). We test these predictions genetically and through analysis of transcription output at ADH1 and at promoters across the genome. Our data support a model whereby ssl2 alleles alter Ssl2 processivity and therefore the probability that TSSs are scanned. Examination of TSS usage genome-wide finds global effects of ssl2 alleles on TSS usage and the potential coupling of Pol II activity and Ssl2/TFIIH processivity during scanning. We propose that the initiation by promoter scanning is determined by the interaction of two functional networks, one controlling initiation efficiency and one controlling the processivity of scanning.

show abstract

Sub1/PC4, a multifaceted factor: from transcription to genome stability

Cited by 29 publications

References 154 publications

Transcriptional positive cofactor 4 promotes breast cancer proliferation and metastasis through c-Myc mediated Warburg effect

Transcriptional positive cofactor 4 promotes breast cancer proliferation and metastasis through c-Myc mediated Warburg effect

Acceleration of ageing via disturbing mTOR‐regulated proteostasis by a new ageing‐associated gene PC4

Ssl2/TFIIH function in Transcription Start Site Scanning by RNA Polymerase II in Saccharomyces cerevisiae

Contact Info

Product

Resources

About