Regulation of the Cyclin-dependent Kinase Inhibitor 1A Gene (CDKN1A) by the Repressor BOZF1 through Inhibition of p53 Acetylation and Transcription Factor Sp1 Binding

Kim, Min-Kyeong; Jeon, Bu‐Nam; Koh, Dong-In; Kim, Kyung‐Sup; Park, So-Yoon; Yun, Chae‐Ok; Hur, Man‐Wook

doi:10.1074/jbc.m112.416297

Cited by 14 publications

(9 citation statements)

References 45 publications

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“…The transcription factors p53 and Sp1 regulate various cell functions, including the promotion of apoptosis, suppression of cell growth, migration, and invasion [ 25 , 26 , 27 ]. To further investigate the underlying molecular mechanisms of CH-5-mediated anticancer activities, the expression level of p53 and Sp1 proteins was examined in U2OS cells treated with CH-5, using Western blotting analysis.…”

Section: Resultsmentioning

confidence: 99%

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

Lima

Seba

Silva

et al. 2018

IJMS

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Curcumin is a potential anticancer drug with poor bioavailability, which limits its clinical use as a therapeutic agent. The aim of this study was a preliminary evaluation of the curcumin analogue CH-5 as a cytotoxic agent in human osteosarcoma cell lines U2OS, MG-63, and Saos-2. CH-5 inhibited cell viability at lower concentrations than curcumin, leading to the induction of apoptosis. The cellular levels of the transcription factors p53 and Sp1 affect the expression of cellular pathways that lead to apoptosis. CH-5 increased p53 protein levels in U2OS cells and reduced Sp1 levels, with a consequent effect on the expression of their target genes DNA methyltransferase 1 (DNMT1) and growth arrest and DNA damage-inducible 45 alpha gene (Gadd45a). CH-5 repressed DNMT1 and increased Gadd45a mRNA expression, which was dependent on p53, as this effect was only observed in the colorectal cancer cell line HCT116 with active p53, but not in the isogenic p53-deficient HCT116 cells. CH-5 also reduced the protein levels of DNMT1, which led to the upregulation of Gadd45a. These results suggest that CH-5 has potentially higher anticancer activity than curcumin, which is associated with the expression of apoptosis-associated genes regulated by the transcription factors Sp1 and p53. Future work on CH-5 will define the therapeutic potential of this compound in vivo.

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Section: Resultsmentioning

confidence: 99%

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

Lima

Seba

Silva

et al. 2018

IJMS

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“…HKR3 Potently Activates Transcription of the ARF Gene-Recently, we found that some POK proteins regulate the cell cycle by controlling the p53 pathway (1)(2)(3)(4)(5). Accordingly, we investigated whether HKR3 inhibited cell proliferation by controlling expression of genes within the ARF-p53 pathway.…”

Section: Journal Of Biological Chemistrymentioning

confidence: 99%

“…POK family proteins, such as ZBTB2, ZBTB5, ZBTB7A(FBI-1), ZBTB7C(KR-POK), and ZBTB8A(BOZF1), were shown to regulate cell cycle and proliferation through the regulation of CDKN1A, a gene member of the p53 pathway (ARF-MDM2-TP53-CDKN1A). CDKN1A encodes the protein p21, which is a negative regulator of the cell cycle (1)(2)(3)(4)(5). In particular, interactions between certain POK family proteins and co-regulators (e.g.…”

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confidence: 99%

Human Krüppel-related 3 (HKR3) Is a Novel Transcription Activator of Alternate Reading Frame (ARF) Gene

Yoon

Choi

Jeon

et al. 2014

Journal of Biological Chemistry

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“…ZNF509L activated transcription of CDKN1A , by binding to its promoter proximal GC boxes and interacting with both MIZ-1 and the co-activator p300 (Figure 8 ) to induce CDKN1A transcription. These proximal GC boxes are the target sites for not only transcription factors like Sp1 but also several other POK family members previously reported as proto-oncoproteins ( 16 , 18 , 30 , 40 , 46 ). Also, oncoproteins that lack direct DNA binding activity to the CDKN1A promoter, including MYC, BCL6 and GFI-1, interact with MIZ-1 to gain promoter access and repress CDKN1A ( 6 , 11 , 13 ).…”

Section: Discussionmentioning

confidence: 99%

Two ZNF509 (ZBTB49) isoforms induce cell-cycle arrest by activating transcription of p21/CDKN1A and RB upon exposure to genotoxic stress

Jeon¹,

Kim²,

Yoon³

et al. 2014

Nucleic Acids Research

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ZNF509 is unique among POK family proteins in that four isoforms are generated by alternative splicing. Short ZNF509 (ZNF509S1, -S2 and -S3) isoforms contain one or two out of the seven zinc-fingers contained in long ZNF509 (ZNF509L). Here, we investigated the functions of ZNF509 isoforms in response to DNA damage, showing isoforms to be induced by p53. Intriguingly, to inhibit proliferation of HCT116 and HEK293 cells, we found that ZNF509L activates p21/CDKN1A transcription, while ZNF509S1 induces RB. ZNF509L binds to the p21/CDKN1A promoter either alone or by interacting with MIZ-1 to recruit the co-activator p300 to activate p21/CDKN1A transcription. In contrast, ZNF509S1 binds to the distal RB promoter to interact and interfere with the MIZF repressor, resulting in derepression and transcription of RB. Immunohistochemical analysis revealed that ZNF509 is highly expressed in normal epithelial cells, but was completely repressed in tumor tissues of the colon, lung and skin, indicating a possible role as a tumor suppressor.

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Regulation of the Cyclin-dependent Kinase Inhibitor 1A Gene (CDKN1A) by the Repressor BOZF1 through Inhibition of p53 Acetylation and Transcription Factor Sp1 Binding

Cited by 14 publications

References 45 publications

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

Human Krüppel-related 3 (HKR3) Is a Novel Transcription Activator of Alternate Reading Frame (ARF) Gene

Two ZNF509 (ZBTB49) isoforms induce cell-cycle arrest by activating transcription of p21/CDKN1A and RB upon exposure to genotoxic stress

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