Translational Repression of G3BP in Cancer and Germ Cells Suppresses Stress Granules and Enhances Stress Tolerance.

Molecular Cell
Anna K LeePatrick Ryan Potts

Abstract

Stress granules (SGs) are membrane-less ribonucleoprotein condensates that form in response to various stress stimuli via phase separation. SGs act as a protective mechanism to cope with acute stress, but persistent SGs have cytotoxic effects that are associated with several age-related diseases. Here, we demonstrate that the testis-specific protein, MAGE-B2, increases cellular stress tolerance by suppressing SG formation through translational inhibition of the key SG nucleator G3BP. MAGE-B2 reduces G3BP protein levels below the critical concentration for phase separation and suppresses SG initiation. Knockout of the MAGE-B2 mouse ortholog or overexpression of G3BP1 confers hypersensitivity of the male germline to heat stress in vivo. Thus, MAGE-B2 provides cytoprotection to maintain mammalian spermatogenesis, a highly thermosensitive process that must be preserved throughout reproductive life. These results demonstrate a mechanism that allows for tissue-specific resistance against stress and could aid in the development of male fertility therapies.

Citations

Sep 15, 2020·The Journal of Biological Chemistry·Rebecca R Florke GeePatrick Ryan Potts
Dec 23, 2020·Journal of Neurochemistry·Hadjara SidibéChristine Vande Velde
Feb 9, 2021·STAR Protocols·Anna K Lee, Patrick Ryan Potts
Jun 20, 2021·Trends in Cancer·Margot LavaléeDon-Marc Franchini

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