ROCK1 promotes B cell differentiation and proteostasis under stress through the heme-regulated proteins, BACH2 and HRI.

ABSTRACT: The mechanisms utilized by differentiating B cells to withstand highly damaging conditions generated during severe infections, like the massive hemolysis that accompanies malaria, are poorly understood. Here, we demonstrate that ROCK1 regulates B cell differentiation in hostile environments replete with pathogen-associated molecular patterns (PAMPs) and high levels of heme by controlling 2 key heme-regulated molecules, BACH2 and heme-regulated eIF2α kinase (HRI). ROCK1 phosphorylates BACH2 and protects it from heme-driven degradation. As B cells differentiate, furthermore, ROCK1 restrains their pro-inflammatory potential and helps them handle the heightened stress imparted by the presence of PAMPs and heme by controlling HRI, a key regulator of the integrated stress response and cytosolic

SUBMITTER: Rivera-Correa J 

PROVIDER: S-EPMC11949073 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature