High mobility group A-interacting proteins in cancer: focus on chromobox protein homolog 7, homeodomain interacting protein kinase 2 and PATZ

Fedele, Monica; Pierantoni, Giovanna Maria; Pallante, Pierlorenzo

doi:10.4081/jnai.2012.3988

Cited by 6 publications

(5 citation statements)

References 83 publications

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“… 22 Similarly, PATZ1 is a transcription factor that binds DNA to specific consensus sequences in promoter regions of several genes. 23 Thus, we asked whether the physical interaction between PATZ1 and p53 takes place on promoter regions of known p53 targets. Therefore, we evaluated whether PATZ1 protein binds the promoters of p53-target genes, such as BAX , MDM2 and CDKN1A , by performing chromatin IP (ChIP) assays.…”

Section: Resultsmentioning

confidence: 99%

“…It has been previously shown that HMGA1, a protein interacting with PATZ1, binds to p53 and inhibits its apoptotic activity. 21 , 23 It would be interesting to determine whether the interaction between PATZ1 and HMGA1 might interfere with the activity of p53. We can hypothesize that in tumours carrying a wt TP53 gene, the balance between HMGA1 and PATZ1 protein levels might have opposite effects on the activity of p53 and, consequently, in tumourigenesis and in response to anticancer treatments.…”

Section: Discussionmentioning

confidence: 99%

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PATZ1 interacts with p53 and regulates expression of p53-target genes enhancing apoptosis or cell survival based on the cellular context

et al. 2013

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PATZ1 is a transcriptional factor functioning either as an activator or a repressor of gene transcription depending upon the cellular context. It appears to have a dual oncogenic/anti-oncogenic activity. Indeed, it is overexpressed in colon carcinomas, and its silencing inhibits colon cancer cell proliferation or increases sensitivity to apoptotic stimuli of glioma cells, suggesting an oncogenic role. Conversely, the development of B-cell lymphomas, sarcomas, hepatocellular carcinomas and lung adenomas in Patz1-knockout (ko) mice supports its tumour suppressor function. PATZ1 role in mouse lymphomagenesis is mainly because of the involvement of PATZ1 in BCL6-negative autoregulation. However, this does not exclude that PATZ1 may be involved in tumorigenesis by other mechanisms. Here, we report that PATZ1 interacts with the tumour suppressor p53 and binds p53-dependent gene promoters, including those of BAX, CDKN1A and MDM2. Knockdown of PATZ1 in HEK293 cells reduces promoter activity of these genes and inhibits their expression, suggesting a role of PATZ in enhancing p53 transcriptional activity. Consistently, Patz1-ko mouse embryonic fibroblasts (MEFs) show decreased expression of Bax, Cdkn1a and Mdm2 compared with wild-type (wt) MEFs. Moreover, Patz1-ko MEFs show a decreased percentage of apoptotic cells, either spontaneous or induced by treatment with 5-fluorouracil (5FU), compared with wt controls, suggesting a pro-apoptotic role for PATZ1 in these cells. However, PATZ1 binds p53-target genes also independently from p53, exerting, in the absence of p53, an opposite function on their expression. Indeed, knockdown of PATZ1 in p53-null osteosarcoma cells upregulates BAX expression and decreases survival of 5FU-treated cells, then suggesting an anti-apoptotic role of PATZ1 in p53-null cancer cells. Therefore, these data support a PATZ1 tumour-suppressive function based on its ability to enhance p53-dependent transcription and apoptosis. Conversely, its opposite and anti-apoptotic role in p53-null cancer cells provides the perspective of PATZ1 silencing as a possible adjuvant in the treatment of p53-null cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

PATZ1 interacts with p53 and regulates expression of p53-target genes enhancing apoptosis or cell survival based on the cellular context

et al. 2013

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“…Based on the results emerged from the present study, we could hypothesize that PATZ1 overexpression may contribute in maintaining the self-renewal and proliferative capacity of GSCs, likely favoring symmetric over asymmetric stem cell division. It is in fact known that both HMGA1 and p53, two PATZ1 interactors (Fedele et al, 2012;Valentino et al, 2013a;Keskin et al, 2015), are deeply involved in the balance between symmetric and asymmetric stem cell division, which plays a key role in the expansion of the stem cell pool in both NSCs and GSCs (Cicalese et al, 2009;Puca et al, 2019). Indeed, an undue increase in NSC symmetrical divisions, due to the disruption of molecular regulators, is the prelude to the conversion to GSCs and tumors in invertebrates (Caussinus and Gonzale, 2005).…”

Section: Discussionmentioning

confidence: 99%

The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation

Mancinelli

Vitiello

Donnini

et al. 2021

Front. Cell Dev. Biol.

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Proper regulation of neurogenesis, the process by which new neurons are generated from neural stem and progenitor cells (NS/PCs), is essential for embryonic brain development and adult brain function. The transcription regulator Patz1 is ubiquitously expressed in early mouse embryos and has a key role in embryonic stem cell maintenance. At later stages, the detection of Patz1 expression mainly in the developing brain suggests a specific involvement of Patz1 in neurogenesis. To address this point, we first got insights in Patz1 expression profile in different brain territories at both embryonic and postnatal stages, evidencing a general decreasing trend with respect to time. Then, we performed in vivo and ex vivo analysis of Patz1-knockout mice, focusing on the ventricular and subventricular zone, where we confirmed Patz1 enrichment through the analysis of public RNA-seq datasets. Both embryos and adults showed a significant reduction in the number of Patz1-null NS/PCs, as well as of their self-renewal capability, compared to controls. Consistently, molecular analysis revealed the downregulation of stemness markers in NS/PCs derived from Patz1-null mice. Overall, these data demonstrate the requirement of Patz1 for NS/PC maintenance and proliferation, suggesting new roles for this key transcription factor specifically in brain development and plasticity, with possible implications for neurodegenerative disorders and glial brain tumors.

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“…Of note, the AT-hook domains of PATZ1 provide a site of undergoing chromatin remodeling, in which proteins bind to DNA during transcription 20 . PATZ1 may have high affinity to GC-rich DNA regions by configurating with its zinc fingers domain 21 . Indeed, our lab have previously identified that the Patz1 has AT-rich or GC-rich binding motif due to its multiple domains 22 .…”

Section: Introductionmentioning

confidence: 99%

POZ/BTB and AT hook containing zinc finger 1 (PATZ1) suppresses differentiation and regulates metabolism in human embryonic stem cells

Huang,

Liao,

Wang

et al. 2024

Int. J. Biol. Sci.

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Human embryonic stem cells (hESCs) can proliferate infinitely (self-renewal) and give rise to almost all types of somatic cells (pluripotency). Hence, understanding the molecular mechanism of pluripotency regulation is important for applications of hESCs in regenerative medicine. Here we report that PATZ1 is a key factor that regulates pluripotency and metabolism in hESCs. We found that depletion of PATZ1 is associated with rapid downregulation of master pluripotency genes and prominent deceleration of cell growth. We also revealed that PATZ1 regulates hESC pluripotency though binding the regulatory regions of OCT4 and NANOG . In addition, we demonstrated PATZ1 is a key node in the OCT4/NANOG transcriptional network. We further revealed that PATZ1 is essential for cell growth in hESCs. Importantly, we discovered that depletion of PATZ1 drives hESCs to exploit glycolysis which energetically compensates for the mitochondrial dysfunction. Overall, our study establishes the fundamental role of PATZ1 in regulating pluripotency in hESCs. Moreover, PATZ1 is essential for maintaining a steady metabolic homeostasis to refine the stemness of hESCs.

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High mobility group A-interacting proteins in cancer: focus on chromobox protein homolog 7, homeodomain interacting protein kinase 2 and PATZ

Cited by 6 publications

References 83 publications

PATZ1 interacts with p53 and regulates expression of p53-target genes enhancing apoptosis or cell survival based on the cellular context

PATZ1 interacts with p53 and regulates expression of p53-target genes enhancing apoptosis or cell survival based on the cellular context

The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation

POZ/BTB and AT hook containing zinc finger 1 (PATZ1) suppresses differentiation and regulates metabolism in human embryonic stem cells

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