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Exoenzyme C3 transferase lowers actin cytoskeleton dynamics, genomic stability and survival of malignant melanoma cells under UV-light stress.
J Photochem Photobiol B. 2020 Jul 02; 209:111947.JP

Abstract

Actin cytoskeleton remodeling is the major motor of cytoskeleton dynamics driving tumor cell adhesion, migration and invasion. The typical RhoA, RhoB and RhoC GTPases are the main regulators of actin cytoskeleton dynamics. The C3 exoenzyme transferase from Clostridium botulinum is a toxin that causes the specific ADP-ribosylation of Rho-like proteins, leading to its inactivation. Here, we examine what effects the Rho GTPase inhibition and the consequent actin cytoskeleton instability would have on the emergence of DNA damage and on the recovery of genomic stability of malignant melanoma cells, as well as on their survival. Therefore, the MeWo cell line, here assumed as a melanoma cell line model for the expression of genes involved in the regulation of the actin cytoskeleton, was transiently transfected with the C3 toxin and subsequently exposed to UV-radiation. Phalloidin staining of the stress fibers revealed that actin cytoskeleton integrity was strongly disrupted by the C3 toxin in association with reduced melanoma cells survival, and further enhanced the deleterious effects of UV light. MeWo cells with actin cytoskeleton previously perturbed by the C3 toxin still showed higher levels and accumulation of UV-damaged DNA (strand breaks and cyclobutane pyrimidine dimers, CPDs). The interplay between reduced cell survival and impaired DNA repair upon actin cytoskeleton disruption can be explained by constitutive ERK1/2 activation and an inefficient phosphorylation of DDR proteins (γH2AX, CHK1 and p53) caused by C3 toxin treatment. Altogether, these results support the general idea that actin network help to protect the genome of human cells from damage caused by UV light through unknown molecular mechanisms that tie the cytoskeleton to processes of genomic stability maintenance.

Authors+Show Affiliations

Biomolecular Systems Signaling Laboratory, Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.Biomolecular Systems Signaling Laboratory, Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.Biomolecular Systems Signaling Laboratory, Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil. Electronic address: flforti@iq.usp.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32652466

Citation

Magalhaes, Yuli T., et al. "Exoenzyme C3 Transferase Lowers Actin Cytoskeleton Dynamics, Genomic Stability and Survival of Malignant Melanoma Cells Under UV-light Stress." Journal of Photochemistry and Photobiology. B, Biology, vol. 209, 2020, p. 111947.
Magalhaes YT, Cardella GD, Forti FL. Exoenzyme C3 transferase lowers actin cytoskeleton dynamics, genomic stability and survival of malignant melanoma cells under UV-light stress. J Photochem Photobiol B, Biol. 2020;209:111947.
Magalhaes, Y. T., Cardella, G. D., & Forti, F. L. (2020). Exoenzyme C3 transferase lowers actin cytoskeleton dynamics, genomic stability and survival of malignant melanoma cells under UV-light stress. Journal of Photochemistry and Photobiology. B, Biology, 209, 111947. https://doi.org/10.1016/j.jphotobiol.2020.111947
Magalhaes YT, Cardella GD, Forti FL. Exoenzyme C3 Transferase Lowers Actin Cytoskeleton Dynamics, Genomic Stability and Survival of Malignant Melanoma Cells Under UV-light Stress. J Photochem Photobiol B, Biol. 2020 Jul 2;209:111947. PubMed PMID: 32652466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exoenzyme C3 transferase lowers actin cytoskeleton dynamics, genomic stability and survival of malignant melanoma cells under UV-light stress. AU - Magalhaes,Yuli T, AU - Cardella,Giovanna D, AU - Forti,Fabio L, Y1 - 2020/07/02/ PY - 2019/12/11/received PY - 2020/05/15/revised PY - 2020/06/26/accepted PY - 2020/7/12/pubmed PY - 2020/7/12/medline PY - 2020/7/12/entrez KW - Actin cytoskeleton KW - DNA damage response and repair KW - Exoenzyme C3 transferase KW - Genomic stability KW - Malignant melanoma MeWo cells KW - Rho GTPase signaling KW - Ultraviolet radiation SP - 111947 EP - 111947 JF - Journal of photochemistry and photobiology. B, Biology JO - J. Photochem. Photobiol. B, Biol. VL - 209 N2 - Actin cytoskeleton remodeling is the major motor of cytoskeleton dynamics driving tumor cell adhesion, migration and invasion. The typical RhoA, RhoB and RhoC GTPases are the main regulators of actin cytoskeleton dynamics. The C3 exoenzyme transferase from Clostridium botulinum is a toxin that causes the specific ADP-ribosylation of Rho-like proteins, leading to its inactivation. Here, we examine what effects the Rho GTPase inhibition and the consequent actin cytoskeleton instability would have on the emergence of DNA damage and on the recovery of genomic stability of malignant melanoma cells, as well as on their survival. Therefore, the MeWo cell line, here assumed as a melanoma cell line model for the expression of genes involved in the regulation of the actin cytoskeleton, was transiently transfected with the C3 toxin and subsequently exposed to UV-radiation. Phalloidin staining of the stress fibers revealed that actin cytoskeleton integrity was strongly disrupted by the C3 toxin in association with reduced melanoma cells survival, and further enhanced the deleterious effects of UV light. MeWo cells with actin cytoskeleton previously perturbed by the C3 toxin still showed higher levels and accumulation of UV-damaged DNA (strand breaks and cyclobutane pyrimidine dimers, CPDs). The interplay between reduced cell survival and impaired DNA repair upon actin cytoskeleton disruption can be explained by constitutive ERK1/2 activation and an inefficient phosphorylation of DDR proteins (γH2AX, CHK1 and p53) caused by C3 toxin treatment. Altogether, these results support the general idea that actin network help to protect the genome of human cells from damage caused by UV light through unknown molecular mechanisms that tie the cytoskeleton to processes of genomic stability maintenance. SN - 1873-2682 UR - https://www.unboundmedicine.com/medline/citation/32652466/Exoenzyme_C3_transferase_lowers_actin_cytoskeleton_dynamics,_genomic_stability_and_survival_of_malignant_melanoma_cells_under_UV-light_stress L2 - https://linkinghub.elsevier.com/retrieve/pii/S1011-1344(20)30397-3 DB - PRIME DP - Unbound Medicine ER -
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