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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Exoenzyme C3 transferase lowers actin cytoskeleton dynamics, genomic stability and survival of malignant melanoma cells under UV-light stress

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Magalhaes, Yuli T. [1] ; Cardella, Giovanna D. [1] ; Forti, Fabio L. [1]
Total Authors: 3
[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Biomol Syst Signaling Lab, Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Web of Science Citations: 0

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 (gamma H2AX, 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. (AU)

FAPESP's process: 17/01451-7 - Investigating Rho GTPases pathways in the response of glioma cell lines to genotoxic stress
Grantee:Yuli Thamires Magalhães
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 19/05736-1 - Study of actin and tubulin cytoskeleton involvement in DNA damage repair of gliomas after gamma radiation treatment
Grantee:Giovanna Duo Cardella
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 15/03983-0 - Molecular and functional investigation of the interactions between DUSP3 with nuclear proteins and its implications in DNA repair mechanisms
Grantee:Fábio Luis Forti
Support Opportunities: Regular Research Grants
FAPESP's process: 18/01753-6 - Identification and functional investigation of proteins that interact with Cdc42 and DUSP12 enzymes in human cells under conditions of genomic instability: a proteomic approach
Grantee:Fábio Luis Forti
Support Opportunities: Regular Research Grants