RASSF1A suppresses the activated K-Ras-induced oxidative DNA damage

Park, Seon Ho; Kim, Jung Jin; Chung, Jin Sil; Lee, So Ra; Lee, Gi Young; Kim, Hyung Jung; Yoo, Young

doi:10.1016/j.bbrc.2011.03.139

Cited by 8 publications

(5 citation statements)

References 28 publications

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“…However, high-throughput sequencing as well as in vitro and in vivo studies have identified oncogene activation as one of the potential causes of DNA damage induction in cancer. Consistent with this idea, the activation of well-characterized oncogenes such as MYC and KRAS has been demonstrated to induce DNA damage via replication and oxidative stress mechanisms (13,14). Furthermore, MYCdriven tumors are dependent on the activity of the DDR kinase checkpoint kinase 1 (CHK1) for their maintenance and growth (15,16).…”

Section: Emerging Evidence For the Role Of Constitutive Dna Damage Inmentioning

confidence: 84%

“…Although the tumorsuppressive role of MYC-induced DDR during the early precancerous stage is well defined, its oncogenic function in the latter stages of cancer has been attributed to MYC-mediated CHK1 regulation, which in turn modulates replication stress in transformed cancer cells (31). However, MYC and other oncogenes, such as RAS, also increase oxidative DNA damage (13,14). Although, in principle, this induced DNA damage could stimulate the various tumor-suppressive pathways to restrict tumor progression, the opposite effect is observed (13).…”

Section: Ramifications Of Distinct Dna Damage Thresholds In Human Canmentioning

confidence: 99%

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DNA Damage in Cancer Therapeutics: A Boon or a Curse?

2015

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Millions of DNA-damaging lesions occur every day in each cell of our bodies due to various stresses. The failure to detect and accurately repair these lesions can give rise to cells with high levels of endogenous DNA damage, deleterious mutations, or genomic aberrations. Such genomic instability can lead to the activation of specific signaling pathways, including the DNA damage response (DDR) pathway. Constitutive activation of DDR proteins has been observed in human tumor specimens from different cancer stages, including precancerous and metastatic cancers, although not in normal tissues. The tumor-suppressive role of DDR activity during the premalignant stage has been studied, and strong evidence is emerging for an oncogenic role for DDR proteins such as DNA-PK and CHK1 during the later stages of tumor development. However, the majority of current cancer therapies induce DNA damage, potentially exacerbating protumorigenic genomic instability and enabling the development of resistance. Therefore, elucidating the molecular basis of DNA damagemediated genomic instability and its role in tumorigenesis is critical. Finally, I discuss the potential existence of distinct DNA damage thresholds at various stages of tumorigenesis and what the ramifications of such thresholds would be, including the ambiguous role of the DDR pathway in human cancers, therapyinduced malignancies, and enhanced therapies.

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Section: Emerging Evidence For the Role Of Constitutive Dna Damage Inmentioning

confidence: 84%

Section: Ramifications Of Distinct Dna Damage Thresholds In Human Canmentioning

confidence: 99%

DNA Damage in Cancer Therapeutics: A Boon or a Curse?

2015

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“…We have shown that re-expression of BLU in NPC, esophageal cancer derived cells inhibits the pathways of JNK and ERK of MAPK family, downregulating the kinase catalyzing protein phosphorylation modification [16]; the axis of MAPK-cyclin D was inhibited, and the cells arrested at G1 phase. The tumor suppressor gene on 3p21, RASSF1A, suppresses tumor formation through negative regulation of oncogene Ras [171], and it has been recognized as the key tumorigenic gene in NPC on mutational or epigenetic inactivation. We have observed that similarly with RASSF1A, BLU/ZMYND10 interferes the activity of mutant Ras to prevent cancer cell proliferation by inhibiting MAPK/ERK signaling [172].…”

Section: Blu/zmynd10 Has Been Shown To Be Downregulated In Tumors Wit...mentioning

confidence: 99%

Zinc finger myeloid Nervy DEAF-1 type (ZMYND) domain containing proteins exert molecular interactions to implicate in carcinogenesis

Huang

Trivedi

et al. 2022

Discov Onc

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Morphogenesis and organogenesis in the low organisms have been found to be modulated by a number of proteins, and one of such factor, deformed epidermal auto-regulatory factor-1 (DEAF-1) has been initially identified in Drosophila. The mammalian homologue of DEAF-1 and structurally related proteins have been identified, and they formed a family with over 20 members. The factors regulate gene expression through association with co-repressors, recognition of genomic marker, to exert histone modification by catalyze addition of some chemical groups to certain amino acid residues on histone and non-histone proteins, and degradation host proteins, so as to regulate cell cycle progression and execution of cell death. The formation of fused genes during chromosomal translocation, exemplified with myeloid transforming gene on chromosome 8 (MTG8)/eight-to-twenty one translocation (ETO) /ZMYND2, MTG receptor 1 (MTGR1)/ZMYND3, MTG on chromosome 16/MTGR2/ZMYND4 and BS69/ZMYND11 contributes to malignant transformation. Other anomaly like copy number variation (CNV) of BS69/ZMYND11 and promoter hyper methylation of BLU/ZMYND10 has been noted in malignancies. It has been reported that when fusing with Runt-related transcription factor 1 (RUNX1), the binding of MTG8/ZMYND2 with co-repressors is disturbed, and silencing of BLU/ZMYND10 abrogates its ability to inhibition of cell cycle and promotion of apoptotic death. Further characterization of the implication of ZMYND proteins in carcinogenesis would enhance understanding of the mechanisms of occurrence and early diagnosis of tumors, and effective antitumor efficacy.

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“…RASSF1A is a tumor suppressor, which regulates several tumor-related signaling pathways and interferes with diverse cellular processes. Previous studies showed that RASSF1A can regulate Ras activation and suppresses oxidative DNA damage and chromosomal damage (Park et al, 2011). It is also phosphorylated by ATM and responding to the DSB damage signals (Hamilton et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Genistein From Fructus sophorae Protects Mice From Radiation-Induced Intestinal Injury

Zhang

Pang²,

Zhang

et al. 2021

Front. Pharmacol.

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The development of an effective pharmacological countermeasure is needed to reduce the morbidity and mortality in high-dose ionizing radiation-induced acute damage. Genistein has shown bioactivity in alleviating radiation damage and is currently synthesized by chemosynthetic methods. Due to concerns about chemical residues and high costs, the clinical application of genistein is still a major challenge. In this study, we aimed to establish an efficient method for the extraction of genistein from Fructus sophorae. The effects of extracted genistein (FSGen) on preventing intestinal injury from radiation were further investigated in this study. C57/BL mice were exposed to 7.5 Gy whole body irradiation with and without FSGen treatments. Histological analysis demonstrated significant structural and functional restitution of the intestine and bone marrow in FSGen-pretreated cohorts after irradiation. Through mRNA expression, protein expression, and small interfering RNA analyses, we demonstrated that FSGen protects IEC-6 cells against radiation damage by upregulating the Rassf1a and Ercc1 genes to effectively attenuate DNA irradiation damage. Together, our data established an effective method to extract genistein from the Fructus sophorae plant with high purity, and validated the beneficial roles of the FSGen in protecting the radiation damage. These results promise the future applications of Fructus sophorae extracted genistein in the protection of radiation related damages.

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RASSF1A suppresses the activated K-Ras-induced oxidative DNA damage

Cited by 8 publications

References 28 publications

DNA Damage in Cancer Therapeutics: A Boon or a Curse?

DNA Damage in Cancer Therapeutics: A Boon or a Curse?

Zinc finger myeloid Nervy DEAF-1 type (ZMYND) domain containing proteins exert molecular interactions to implicate in carcinogenesis

Genistein From Fructus sophorae Protects Mice From Radiation-Induced Intestinal Injury

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