The PI3K/Akt1 pathway enhances steady state levels of FANCL

Abstract

Fanconi anemia hematopoietic stem cells display poor self-renewal capacity when subjected to a variety of cellular stress. This phenotype raises the question whether the Fanconi anemia proteins are stabilized or recruited as part of a stress response and protect against stem cell loss. Here we provide evidence that FANCL, the E3 ubiquitin ligase of the Fanconi anemia pathway, is constitutively targeted for degradation by the proteosome. We confirm biochemically that FANCL is poly-ubiquitinated with lysine-48 linked chains.