Two c-Myc binding sites are crucial in upregulating the expression of human phospholipid scramblase 1 gene

Vinnakota, Janaki Manoja; Gummadi, Sathyanarayana N.

doi:10.1016/j.bbrc.2015.11.131

Cited by 12 publications

(8 citation statements)

References 27 publications

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“…c-Myc is a protooncogene that plays a nonnegligible role in cell cycle regulation, apoptosis, and tumorigenesis [14,19]. Studies have reported that transcription factors such as hPLSCR1, E2F4, RBM38, BRD4, and hZαADAR1 can regulate c-Myc expression via directly binding to its promoter region [20][21][22][23][24]. Several key target genes of c-Myc have been identified, including cyclins and cyclin-dependent kinases (Cdks) [25].…”

Section: Discussionmentioning

confidence: 99%

THAP11 Functions as a Tumor Suppressor in Gastric Cancer through Regulating c-Myc Signaling Pathways

Zhang

Shi

et al. 2020

BioMed Research International

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We aim to investigate the role of THAP11 (thanatos-associated protein11) in gastric cancer and its regulation mechanisms. THAP11 expression was analyzed in 51 pairs of GC tissues and the corresponding paracancerous tissues by qRT-PCR and Western blot. After THAP11 was overexpressed or knocked-down, cell proliferation, cell cycle, and apoptosis were detected in MKN-45 cells. We found that THAP11 was significantly downregulated in GC tissues and GC cell lines. Functionally, THAP11 overexpression markedly inhibited cell growth, induced G1/G0 cell-cycle arrest, and promoted cell apoptosis of MKN-45 cells, while silencing of THAP11 led to increased cell growth, increased DNA synthesis, and inhibited apoptosis. In addition, THAP11 negatively regulated the expression of c-Myc, decreased cyclinD1 protein, and increased p27 and p21 protein levels. We also found cell growth suppression induced by THAP11 was rescued by c-Myc overexpression, further confirming that THAP11 suppresses gastric cancer cell growth via the c-Myc pathway. THAP11 acts as a cell growth suppressor and exerts its role possibly through negatively regulating c-Myc pathway in gastric cancer.

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Section: Discussionmentioning

confidence: 99%

THAP11 Functions as a Tumor Suppressor in Gastric Cancer through Regulating c-Myc Signaling Pathways

Zhang

Shi

et al. 2020

BioMed Research International

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“…Both in silico and in vivo analysis shows that c-Myc is a transcriptional regulator of PLSCR1 with a putative binding site located between −800 and −400 upstream of 5’ the flanking region of PLSCR1 ( Vinnakota and Gummadi, 2016 ). Both PLSCR1 and PLSCR4 are down regulated at mRNA and protein level by a Snail transcription factor (Snail TF) that binds to the putative promoter regions of PLSCR1 [−1,525 to −1,244] and PLSCR4 [−1,521 to −1,516] respectively ( Francis et al, 2014 ; Vinnakota and Gummadi, 2016 ). This finding demonstrates key regulatory role of PLSCRs in tumorigenesis.…”

Section: Transcriptional Regulation Of Scramblase Expression During M...mentioning

confidence: 99%

Phospholipid Scramblases: Role in Cancer Progression and Anticancer Therapeutics

2022

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Phospholipid scramblases (PLSCRs) that catalyze rapid mixing of plasma membrane lipids result in surface exposure of phosphatidyl serine (PS), a lipid normally residing to the inner plasma membrane leaflet. PS exposure provides a chemotactic eat-me signal for phagocytes resulting in non-inflammatory clearance of apoptotic cells by efferocytosis. However, metastatic tumor cells escape efferocytosis through alteration of tumor microenvironment and apoptotic signaling. Tumor cells exhibit altered membrane features, high constitutive PS exposure, low drug permeability and increased multidrug resistance through clonal evolution. PLSCRs are transcriptionally up-regulated in tumor cells leading to plasma membrane remodeling and aberrant PS exposure on cell surface. In addition, PLSCRs interact with multiple cellular components to modulate cancer progression and survival. While PLSCRs and PS exposed on tumor cells are novel drug targets, many exogenous molecules that catalyze lipid scrambling on tumor plasma membrane are potent anticancer therapeutic molecules. In this review, we provide a comprehensive analysis of scramblase mediated signaling events, membrane alteration specific to tumor development and possible therapeutic implications of scramblases and PS exposure.

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“…This elevated expression of PLSCR1 in EBV-infected NPC cells may not arise from EBV infection but from these cells' epidermal origin. c-Myc has been suggested to up-regulate the expression of PLSCR1 by directly binding to its promoter in HEK-293 cells (37). c-Myc is also known to be predominantly expressed in the basal cell layers of the epidermis and is constitutively expressed in mouse primary keratinocytes (38,39).…”

Section: Plscr1 Represses Ebv Bzlf1-dependent Lytic Transcriptionmentioning

confidence: 99%

Interaction of phospholipid scramblase 1 with the Epstein-Barr virus protein BZLF1 represses BZLF1-mediated lytic gene transcription

Kusano

Ikeda

2019

Journal of Biological Chemistry

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Human phospholipid scramblase 1 (PLSCR1) is strongly expressed in response to interferon (IFN) treatment and viral infection, and PLSCR1 has been suggested to play an important role in IFN-dependent antiviral responses. In this study, we showed that the basal expression of PLSCR1 was significantly elevated in Epstein-Barr virus (EBV)-infected nasopharyngeal carcinoma (NPC). PLSCR1 was observed to directly interact with the EBV immediate-early transactivator BZLF1 in vitro and in vivo, and this interaction repressed the BZLF1-mediated transactivation of an EBV lytic BMRF1 promoter construct. In addition, PLSCR1 expression decreased the BZLF1-mediated up-regulation of lytic BMRF1 mRNA and protein expression in WT and PLSCR1-knockout EBV-infected NPC cells. Furthermore, we showed that PLSCR1 represses the interaction between BZLF1 and CREB-binding protein (CBP), which enhances the BZLF1-mediated transactivation of EBV lytic promoters. These results reveal for the first time that PLSCR1 specifically interacts with BZLF1 and negatively regulates its transcriptional regulatory activity by preventing the formation of the BZLF1-CBP complex. This interaction may contribute to the establishment of latent EBV infection in EBV-infected NPC cells.

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Two c-Myc binding sites are crucial in upregulating the expression of human phospholipid scramblase 1 gene

Cited by 12 publications

References 27 publications

THAP11 Functions as a Tumor Suppressor in Gastric Cancer through Regulating c-Myc Signaling Pathways

THAP11 Functions as a Tumor Suppressor in Gastric Cancer through Regulating c-Myc Signaling Pathways

Phospholipid Scramblases: Role in Cancer Progression and Anticancer Therapeutics

Interaction of phospholipid scramblase 1 with the Epstein-Barr virus protein BZLF1 represses BZLF1-mediated lytic gene transcription

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