Alla Grishok | PubMed Health

PubMed2026

Spermatogenesis-specific Argonautes ALG-3/4 promote LEA-1 expression in oocytes.

Small interfering RNAs bound to Argonautes ALG-3 and ALG-4 ( ALG-3 /4) in spermatocytes regulate fertility and aging in C. elegans . ALG-3 /4 cell non-autonomously repress DAF-18 /PTEN in the oocyte, thereby limiting the activity of DAF-16 /FOXO and longevity. We find that the DAF-16 and ALG-3 /4 target gene lea-1 is downregulated in precursor germ cells and oocytes of alg-3 /4 mutants while being upregulated in age-1 ( hx546 ) PI3K mutants, where DAF-16 is activated. The downregulation of lea-1 in alg-3 /4 mutants is inherited, unlike the elevation in DAF-18 levels. We therefore propose that ALG-3 /4 regulate LEA-1 and DAF-18 through distinct non-autonomous mechanisms.

Journal Article↗

PubMed2026

Proteolytic activation of c-MYC facilitated by DOT1L.

c-MYC is a key regulator of growth and metabolism. Functional and molecular cooperation between the H3K79 methyltransferase DOT1L and c-MYC has been reported in several human cancer types, but the nature of their interaction remains undefined. We demonstrate that DOT1L and MYC [Myc and Mondo-like (MML-1) in Caenorhabditis elegans] coregulate genes in the nematode model and mammalian cancer cells. Moreover, both c-MYC and MML-1 exhibit cleavage products facilitated by DOT1L function. Surprisingly, we found a similarity between a conserved sequence in DOT1 proteins and the DDI-family protease catalytic motif. We characterize a c-MYC sequence preceding the DNA-binding domain as a site of nuclear proteolytic cleavage, demonstrate its importance for transcription activation by c-MYC, and propose that c-MYC is activated by a protease, as previously reported for Nuclear factor erythroid 2-related factor (NRF) and SREBP transcription factors. Our results suggest that DOT1L may activate c-MYC and other transcription factors in the nucleus by acting as a protease.

Animals↗