Emerging roles of activating transcription factor (ATF) family members in tumourigenesis and immunity: Implications in cancer immunotherapy

Chen, Meilin; Liu, Yijun; Yang, Yuqin; Qiu, Yanbing; Wang, Zhicheng; Li, Xiaoxu; Zhang, Wenling

doi:10.1016/j.gendis.2021.04.008

Cited by 58 publications

(40 citation statements)

References 165 publications

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“…We observe that many TFs have cell type specific binding patterns at differing degrees of specificity, where 10 Figure 3b shows a histogram of the distribution of AUC differences between Cell Type General and Cell Type Specific across the different TF and AB combinations, with the bins containing ATF7, CTCF, HCFC1, BACH1, MYC and SOX6 highlighted in red. TFs that play a pivotal role in cancer either as oncogenes or suppressors, such as MYC [52,53,54,55], BACH1 [56,57,58], ATF7 [45,46,47,48], and SOX6 [59,60], show a relatively higher cell type specificity than other TFs, such as CTCF [49,50,51] and HCFC1 [61,62,63], that are involved in chromatin regulation or other cellular processes. SI Table 1 shows the AUC differences obtained for each TF-AB.…”

Section: Resultsmentioning

confidence: 99%

“…To demonstrate our approach, we first focus on Activating Transcription Factor 7 (ATF7). As a member of the ATF family, ATF7 binds to the cyclic AMP response element (CRE) with the consensus DNA sequence “TGACGTCA” [45, 46]. Members of the ATF family are basic leucine zipper (bZIP) factors that complex with other bZIP factors to form homodimers or heterodimers [45, 46, 47, 48].…”

Section: Resultsmentioning

confidence: 99%

“…As a member of the ATF family, ATF7 binds to the cyclic AMP response element (CRE) with the consensus DNA sequence “TGACGTCA” [45, 46]. Members of the ATF family are basic leucine zipper (bZIP) factors that complex with other bZIP factors to form homodimers or heterodimers [45, 46, 47, 48]. The ATF TFs exhibit varying functionalities in different tissues and cancerous cell lines, including tumour suppressive and oncogenic functions [46].…”

Section: Resultsmentioning

confidence: 99%

“…Members of the ATF family are basic leucine zipper (bZIP) factors that complex with other bZIP factors to form homodimers or heterodimers [45, 46, 47, 48]. The ATF TFs exhibit varying functionalities in different tissues and cancerous cell lines, including tumour suppressive and oncogenic functions [46]. For instance, the deletion of ATF7 results in the spread of lymphoma [46].…”

Section: Resultsmentioning

confidence: 99%

“…The ATF TFs exhibit varying functionalities in different tissues and cancerous cell lines, including tumour suppressive and oncogenic functions [46]. For instance, the deletion of ATF7 results in the spread of lymphoma [46]. Conversely, the activation of ATF7 in gastric or hepatocellular carcinoma promotes the proliferation of cancer cells.…”

Section: Resultsmentioning

confidence: 99%

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Cell Type Specific DNA Signatures of Transcription Factor Binding

Turcotte

Perkins

2022

Preprint

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Transcription factors (TFs) bind to different parts of the genome in different types of cells. These differences may be due to alterations in the DNA-binding preferences of a TF itself, or mechanisms such as chromatin accessibility, steric hindrance, or competitive binding, that result in a DNA "signature" of differential binding. We propose a method called SigTFB (Signatures of TF Binding), based on deep learning, to detect and quantify cell type specificity in a TF's DNA-binding signature. We conduct a wide scale investigation of 194 distinct TFs across various cell types. We demonstrate the existence of cell type specificity in approximately 30% of the TFs. We stratify our analysis by different antibodies for the same TF, to rule out the possibility of certain technical artifacts, yet we find that cell type specificity estimates are largely consistent when the same TF is assayed with different antibodies. To further explain the biology behind a TF's cell type specificity, or lack thereof, we conduct a wide scale motif enrichment analysis of all TFs in question. We show that the presence of alternate motifs correlates with a higher degree of cell type specificity in TFs, such as ATF7, while finding consistent motifs throughout is usually associated with the absence of cell type specificity in a TF, such as CTCF. In particular, we observe that several important TFs show distinct DNA binding signatures in different cancer cell types, which may point to important differences in modes of action. Moreover, we find that motif enrichment sometimes correlates with gene expression in TFs with higher cell type specificity. Our comprehensive investigation provides a basis for further study of the mechanisms behind differences in TF-DNA binding in different cell types.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Cell Type Specific DNA Signatures of Transcription Factor Binding

Turcotte

Perkins

2022

Preprint

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Transcription factor Atf1‐dependent degradation of the mitotic cyclin Cdc13 is regulated by multiple factors in Schizosaccharomyces pombe

et al. 2022

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The bZIP transcription factor Atf1 is a key player in the transcriptional programme of Schizosaccharomyces pombe cell cycle. It also controls both expression and degradation of mitotic cyclin Cdc13. Temporal regulation of these opposing functions of Atf1 is critical for fidelity of cell division. Our investigations revealed that an increase in the activity of mitogen-activated protein kinase (MAPK) Spc1 during mitotic exit and the consequent phosphorylation of Atf1 along with the prevailing high activity of cyclin-dependent kinase Cdc2 regulate Cdc13 degradation. Our results also indicate the possibility of a complex interplay between Cdc2 inhibitory kinase Wee1, the anaphase-promoting complex and Atf1 during mitotic exit. These observations provide evidence of new regulatory mechanisms of mitotic exit.

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m⁶A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways

Wu,

Wang,

Pan

et al. 2024

Advanced Science

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Colorectal cancer (CRC) is the third most common cancer type and the second highest mortality rate among cancers. However, the mechanisms underlying CRC progression remain to be fully understood. In this work, a recently identified m6A‐modified RNA reader protein Proline‐rich Coiled‐coil 2a (PRRC2A) is markedly upregulated in CRC, and intestinal epithelium‐specific deletion of Prrc2a significantly suppressed tumor cell growth, stemness, and migratory capacity, while its overexpression promoted these behaviors. Through multiomics analysis, PRRC2A directly targeted CSNK1E (encoding CK1ε), maintaining its RNA stability in an m6A‐dependent manner, and that elevated CK1ε can concomitantly result in activation of the WNT and YAP signaling pathways. Interestingly, PRRC2A is directly regulated by the transcription factor ATF1 in its promoter. In summary, the work reveals a novel mechanism by which m6A reader PRRC2A promotes colorectal cancer progression via CK1ε and aberrant upregulation of WNT and YAP signaling. Therefore, PRRC2A and CK1ε can be potential therapeutic targets for treating CRC.

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Emerging roles of activating transcription factor (ATF) family members in tumourigenesis and immunity: Implications in cancer immunotherapy

Cited by 58 publications

References 165 publications

Cell Type Specific DNA Signatures of Transcription Factor Binding

Cell Type Specific DNA Signatures of Transcription Factor Binding

Transcription factor Atf1‐dependent degradation of the mitotic cyclin Cdc13 is regulated by multiple factors in Schizosaccharomyces pombe

m⁶A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways

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Emerging roles of activating transcription factor (ATF) family members in tumourigenesis and immunity: Implications in cancer immunotherapy

Cited by 58 publications

References 165 publications

Cell Type Specific DNA Signatures of Transcription Factor Binding

Cell Type Specific DNA Signatures of Transcription Factor Binding

Transcription factor Atf1‐dependent degradation of the mitotic cyclin Cdc13 is regulated by multiple factors in Schizosaccharomyces pombe

m6A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways

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m⁶A Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε‐Mediated Activation of WNT and YAP Signaling Pathways