ALG-2/AGO-Dependent mir-35 Family Regulates DNA Damage-Induced Apoptosis Through MPK-1/ERK MAPK Signaling Downstream of the Core Apoptotic Machinery in Caenorhabditis elegans.
Markus Alexander DollNajmeh SoltanmohammadiBjörn SchumacherPublished in: Genetics (2019)
MicroRNAs (miRNAs) associate with argonaute (AGO) proteins to post-transcriptionally modulate the expression of genes involved in various cellular processes. Herein, we show that loss of the Caenorhabditis elegans AGO gene alg-2 results in rapid and significantly increased germ cell apoptosis in response to DNA damage inflicted by ionizing radiation (IR). We demonstrate that the abnormal apoptosis phenotype in alg-2 mutant animals can be explained by reduced expression of mir-35 miRNA family members. We show that the increased apoptosis levels in IR-treated alg-2 or mir-35 family mutants depend on a transient hyperactivation of the C. elegans ERK1/2 MAPK ortholog MPK-1 in dying germ cells. Unexpectedly, MPK-1 phosphorylation occurs downstream of caspase activation and depends at least in part on a functional cell corpse-engulfment machinery. Therefore, we propose a refined mechanism, in which an initial proapoptotic stimulus by the core apoptotic machinery initiates the engulfment process, which in turn activates MAPK signaling to facilitate the demise of genomically compromised germ cells.
Keyphrases
- induced apoptosis
- oxidative stress
- signaling pathway
- cell proliferation
- dna damage
- pi k akt
- cell cycle arrest
- endoplasmic reticulum stress
- long non coding rna
- cell death
- poor prognosis
- long noncoding rna
- dna repair
- single cell
- mesenchymal stem cells
- bone marrow
- anti inflammatory
- cell therapy
- binding protein
- stem cells
- blood brain barrier
- dna methylation
- newly diagnosed
- quantum dots
- transcription factor
- subarachnoid hemorrhage
- living cells
- wild type
- loop mediated isothermal amplification