Conservation analysis of core cell cycle regulators and their transcriptional behavior during limb regeneration in Ambystoma mexicanum

Espinal-Centeno, Annie; Dipp-Álvarez, Melissa; Saldaña, Carlos; Bako, L.; Cruz‐Ramírez, Alfredo

doi:10.1016/j.mod.2020.103651

Cited by 8 publications

(10 citation statements)

References 53 publications

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“…p15 and p16 sequences did not clearly separate in our analysis, and therefor are reported together. This agrees with past phylogenetic analysis (57), wherein the p18 and p19 sequences, which are the more ancestral sequences of the family, form independent clades that then cluster together separately from the p15/p16 clade. This difference between the two sequences is largely due to a large deletion in p15 and p16.…”

Section: Resultssupporting

confidence: 91%

“…A total of 654 sequences were analyzed to form a neighbor-joining tree ( Fig 6 ). We were able to identify p15/p16 ( Supplementary File 6 ) and p18 sequences ( Supplementary File 7 ) in all classes of jawed vertebrates, but we only identified p19 ( Supplementary File 8 ) sequences in osteichthyians, amphibians, reptiles, and mammals, which is consistent with previous literature which notes the loss of p19 in avian species and has not observed p19 in chondrichthyan species (57). p15 and p16 sequences did not clearly separate in our analysis, and therefor are reported together.…”

Section: Resultssupporting

confidence: 90%

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Phylogenetic analysis of the MCL1 BH3 binding groove and rBH3 sequence motifs in the p53 and INK4 protein families

Placzek

McGriff

2022

Preprint

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B-cell lymphoma 2 (Bcl-2) proteins are central, conserved regulators of apoptosis. Bcl-2 family function is regulated by binding interactions between the Bcl-2 homology 3 (BH3) motif in pro-apoptotic family members and the BH3 binding groove found in both the pro-apoptotic effector and anti-apoptotic Bcl-2 family members. A novel motif, the reverse BH3 (rBH3), has been shown to interact with the anti-apoptotic Bcl-2 homolog MCL1 (Myeloid cell leukemia 1) and have been identified in the p53 homolog p73, and the CDK4/6 (cyclin dependent kinase 4/6) inhibitor p18INK4c, (p18, cyclin-dependent kinase 4 inhibitor c). To determine the conservation of rBH3 motif, we first assessed conservation of MCL1's BH3 binding groove, where the motif binds. We then constructed neighbor-joining phylogenetic trees of the INK4 and p53 protein families and analyzed sequence conservation using sequence logos of the rBH3 locus. This showed the rBH3 motif is conserved throughout jawed vertebrates p63 and p73 sequences and in chondrichthyans, amphibians, mammals, and some reptiles in p18. Finally, a potential rBH3 motif was identified in mammalian and osteichthyan p19INK4d (p19, cyclin dependent kinase 4 inhibitor d). These findings demonstrate that the interaction between MCL1 and other cellular proteins mediated by the rBH3 motif may be conserved throughout jawed vertebrates.

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 90%

Phylogenetic analysis of the MCL1 BH3 binding groove and rBH3 sequence motifs in the p53 and INK4 protein families

Placzek

McGriff

2022

Preprint

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“…Recently, a complete transcriptional behavior of key regulatory factors of the cell cycle in axolotl was recently reported by Espinal‐Centeno who performed RT‐qPCR analyses in blastema stages and showed that both transcription activation and repression of transcriptional factors occur in a timely manner. Interestingly, the authors demonstrate that E2F3B and p16 homologous genes are not present in the axolotl, suggesting that this could be related to the resistance to carcinogenesis, which remains to be experimentally tested (Espinal‐Centeno et al, 2020).…”

Section: Possible Molecular Mechanisms That Could Reduce Cancer Susce...mentioning

confidence: 99%

Cancer in Amphibia, a rare phenomenon?

Torres‐Dimas¹,

Cruz‐Ramírez²,

Bermúdez‐Cruz³

2022

Cell Biology International

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Compared to other animals, the spontaneous occurrence of tumors in wild amphibians is relatively rare, generally limited to specific populations or species.The number of reports of spontaneous tumors in amphibians known up to 1986 was 491 cases in anurans and about 253 cases in urodeles. Similarly, there have been many, unsuccessful attempts to chemically or biologically induce tumors in amphibians. With these considerations, it is inevitable to wonder: do urodeles and anurans have an inherent resistance to cancer? Here, we review the spontaneous and induced occurrence of tumors in amphibians in a timeline, as well as failed attempts to induce tumors in these amphibians. Indeed, recent studies seem to indicate that there is a relationship between regeneration and cancer because regenerating tissues seem to resist tumorigenesis, as opposed to nonregenerative tissues of the same amphibian models. Although the mechanisms that allow regenerating tissues to resist tumorigenesis have not been elucidated, it is worth to note that, in addition to the apparent relationship between regeneration and cancer, amphibians possess characteristics that could contribute to their ability to resist the development of neoplastic events. The implications of these features in cancer susceptibility are discussed.

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“…5,10,11 A vast cellular activation and proliferation characterize tissue regeneration in the axolotl; this correlates with the high transcription of genes involved in cell cycle progression and reports on the acceleration of the cell cycle. 12,13 In this context, the inheritance of correct genetic information through consecutive cell divisions is imperative to secure proper regeneration and tissue functionality. Consequently, to maintain genome stability along the DNA replication process during the highly proliferative regeneration, the axolotl must be equipped with specialized and coordinated molecular systems.…”

Section: Introductionmentioning

confidence: 99%

“…A vast cellular activation and proliferation characterize tissue regeneration in the axolotl; this correlates with the high transcription of genes involved in cell cycle progression and reports on the acceleration of the cell cycle 12,13 . In this context, the inheritance of correct genetic information through consecutive cell divisions is imperative to secure proper regeneration and tissue functionality.…”

Section: Introductionmentioning

confidence: 99%

Evidence of requirement for homologous‐mediated DNA repair during Ambystoma mexicanum limb regeneration

García-Lepe

Torres‐Dimas

Espinal-Centeno

et al. 2022

Developmental Dynamics

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Background Limb regeneration in the axolotl is achieved by epimorphosis, thus depending on the blastema formation, a mass of progenitor cells capable of proliferating and differentiating to recover all lost structures functionally. During regeneration, the blastema cells accelerate the cell cycle and duplicate its genome, which is inherently difficult to replicate because of its length and composition, thus being prone to suffer double‐strand breaks. Results We identified and characterized two remarkable components of the homologous recombination repair pathway (Amex.RAD51 and Amex.MRE11), which were heterologously expressed, biochemically characterized, and inhibited by specific chemicals. These same inhibitors were applied at different time points after amputation to study their effects during limb regeneration. We observed an increase in cellular senescent accompanied by a slight delay in regeneration at 28 days postamputation regenerated tissues; moreover, inhibitors caused a rise in the double‐strand break signaling as a response to the inhibition of the repair mechanisms. Conclusions We confirmed the participation and importance of homologous recombination during limb regeneration. The chemical inhibition induces double‐strand breaks that lead to DNA damage associated senescence, or in an alternatively way, this damage could be possibly repaired by a different DNA repair pathway, permitting proper regeneration and avoiding senescence.

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Conservation analysis of core cell cycle regulators and their transcriptional behavior during limb regeneration in Ambystoma mexicanum

Cited by 8 publications

References 53 publications

Phylogenetic analysis of the MCL1 BH3 binding groove and rBH3 sequence motifs in the p53 and INK4 protein families

Phylogenetic analysis of the MCL1 BH3 binding groove and rBH3 sequence motifs in the p53 and INK4 protein families

Cancer in Amphibia, a rare phenomenon?

Evidence of requirement for homologous‐mediated DNA repair during Ambystoma mexicanum limb regeneration

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