Modulator of Apoptosis 1 (MOAP-1) Is a Tumor Suppressor Protein Linked to the RASSF1A Protein

Law, Jennifer; Salla, Mohamed; Zare, Alaa; Wong, Yoke; Luong, Le Anh; Volodko, Natalia; Svystun, Orysya; Flood, Kayla; Lim, Jue Tao; Sung, Miranda M.; Dyck, Jason R.B.; Tan, Chong Teik; Su, Y. K.; Yu, Victor C.; Mackey, John R.; Baksh, Shairaz

doi:10.1074/jbc.m115.648345

Cited by 36 publications

(32 citation statements)

References 57 publications

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“…MOAP-1 is a regulator of the apoptotic executor Bax [48] and has tumor suppressor properties [49]. Activated Ras enhances the interaction between RASSF1A and MOAP-1 and this leads to Bax activation [46], translocation to mitochondria and apoptosis [47].…”

Section: Rassf1mentioning

confidence: 99%

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Ras signaling through RASSF proteins

Donninger

Schmidt

Mezzanotte

et al. 2016

Seminars in Cell & Developmental Biology

107

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There are six core RASSF family proteins that contain conserved Ras Association domains and may serve as Ras effectors. They lack intrinsic enzymatic activity and appear to function as scaffolding and localization molecules. While initially being associated with pro-apoptotic signaling pathways such as Bax and Hippo, it is now clear that they can also connect Ras to a surprisingly broad range of signaling pathways that control senescence, inflammation, autophagy, DNA repair, ubiquitination and protein acetylation. Moreover, they may be able to impact the activation status of pro-mitogenic Ras effector pathways, such as the Raf pathway. The frequent epigenetic inactivation of RASSF genes in human tumors disconnects Ras from pro-death signaling systems, enhancing Ras driven transformation and metastasis. The best characterized members are RASSF1A and RASSF5 (NORE1A).

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Section: Rassf1mentioning

confidence: 99%

“…This is a Bax activating event. This whole process may involve positive feedback loops, as over-expression of MOAP-1 leads to upregulation of MST1 [49]. …”

Section: Rassf1mentioning

confidence: 99%

Ras signaling through RASSF proteins

Donninger

Schmidt

Mezzanotte

et al. 2016

Seminars in Cell & Developmental Biology

107

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“…The two validated targets of miR-1228 identified using the miRTargetLink database might have important relevance in colorectal cancer ( Figure 4E). The first gene, MOAP1, has been previously identified as an important tumor suppressor molecule linked to the RASSF1A protein, with implications in apoptosis [41]. Data from The Human Protein Atlas [42] reveal that this protein is actually downregulated in colorectal cancer patients; the fact is that, in some instances, this can be contradictable with miR-1228-3p expression (which is also downregulated in tumor tissue).…”

Section: Discussionmentioning

confidence: 99%

Plasma and Tissue Specific miRNA Expression Pattern and Functional Analysis Associated to Colorectal Cancer Patients

Cojocneanu

Braicu

Ráduly

et al. 2020

Cancers

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An increasing number of studies suggest the implication of microRNAs (miRNAs) in colorectal (CRC) carcinogenesis and disease progression. Nevertheless, the basic mechanism is not yet clear. We determined plasma miRNA expression levels using Agilent microarray technology followed by overlapping with The Cancer Genome Atlas (TCGA) tissue data and a qRT-PCR validation step and analysis of the altered miRNA signatures to emphasize new mechanistic insights. For TGCA dataset, we identified 156 altered miRNAs (79 downregulated and 77 upregulated) in colorectal tissue samples versus normal tissue. The microarray experiment is based on 16 control samples, 38 CRC plasma samples from colorectal cancer patients who have not undergone chemotherapy, and 17 chemo-treated samples. In the case of the analysis of CRC cancer versus healthy control we identified 359 altered miRNAs (214 downregulated and 60 upregulated), considering as the cutoff value a fold-change of ±1.5 and p < 0.01. An additional microarray analysis was performed on plasma from untreated colorectal cancer (n = 38) and chemotherapy-treated colorectal cancer patients (n = 17), which revealed 15 downregulated miRNAs and 53 upregulated miRNAs, demonstrating that the plasma miRNA pattern is affected by chemotherapy and emphasizing important regulators of drug resistance mechanisms. For the validation of the microarray data, we selected a panel of 4 miRNAs from the common miRNA signatures for colon and rectal cancer (miR-642b-3p, miR-195-5p and miR-4741). At the tissue level, the expression levels were in agreement with those observed in colorectal plasma. miR-1228-3p, the top upregulated miRNA in CRC, was chosen to be validated on tissue and plasma samples, as it was demonstrated to be downregulated at tissue level in our patient cohort. This was confirmed by TCGA data and was one example of ta ranscript that has a different expression level between tumor tissue and plasma. Developing more efficient investigation methods will help explain the mechanisms responsible for miRNAs released in biofluids, which is the most upregulated transcript in colorectal plasma samples and which can function as a prediction tool within the oncological field.

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“…LCE1F protein interacts with protein arginine methyltransferase 5 (PRMT5) in response to DNA damage [10]. MOAP1 participates in the internal and external pathways of cell death and activates the apoptotic protein BAX of Bcl-2 family [25]. Studies have shown that knockout of EIF3D significantly induces G2/M arrest and apoptosis by down-regulating cyclin B1 and upregulating p21 [26].…”

Section: Discussionmentioning

confidence: 99%

“…(a) 15 genes such as apoptotic regulator 1 (MOAP1) and eukaryotic translation initiation factor 3 subunit D (EIF3D) that were reported to regulate cell cycle, apoptosis, and cell death [25,26]. USP17L6P had a positive regulation relationship with TP53-regulated inhibitor of apoptosis (TRIAP1) that was associated with apoptosis and cell death [27].…”

Section: Coexpression Networkmentioning

confidence: 99%

The Potential Regulatory Roles of lncRNAs in DNA Damage Response in Human Lymphocytes Exposed to UVC Irradiation

Wang

et al. 2020

BioMed Research International

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Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that modulate gene expression, thereby participating in the regulation of various cellular processes. However, it is not clear about the expression and underlying mechanism of lncRNAs in irradiation-induced DNA damage response. In the present study, we performed integrative analysis of lncRNA-mRNA expression profile in human lymphocytes irradiated with ultraviolet-C (UVC). The results showed that exposure to UVC irradiation dose-dependently increased the fluorescence intensity of γ-H 2 AX and induced cell death. Microarray analysis revealed that up-regulated lncRNAs were more common than down-regulated lncRNAs with the increase of radiation dose in UVC-radiated cells. Stem analysis demonstrated the relationship between lncRNA expression level and radiation dose. qPCR results confirmed that LOC338799 and its coexpressed genes such as LCE1F and ISCU showed the increase in expression levels with the increase of UVC radiation dose. We utilized Cytoscape to screen out 5 lncRNAs and 13 coexpressed genes linking to p53, which might participate in the regulation of DNA damage, cell cycle arrest, apoptosis, and cell death. These findings suggest that lncRNAs might play a role in UVC-induced DNA damage response through regulating expression of genes in p53 signaling pathway.

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Modulator of Apoptosis 1 (MOAP-1) Is a Tumor Suppressor Protein Linked to the RASSF1A Protein

Cited by 36 publications

References 57 publications

Ras signaling through RASSF proteins

Ras signaling through RASSF proteins

Plasma and Tissue Specific miRNA Expression Pattern and Functional Analysis Associated to Colorectal Cancer Patients

The Potential Regulatory Roles of lncRNAs in DNA Damage Response in Human Lymphocytes Exposed to UVC Irradiation

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