The Hace1 E3 Ligase Modulates the Activity of Multiple Tumor Suppressive CRL E3 Ligases by binding to CAND1

ABSTRACT: The Hace1 E3 ligase is a tumor suppressor in stressed cells. Through unknown mechanisms, Hace1 indirectly targets the cyclin D1 proto-oncogene for proteasomal degradation during nutrient depletion. We now show that Hace1 targets HIF1alpha for VHL-dependent degradation during hypoxia. To better understand these diverse actions we performed mass spectrometry to identify Hace1-interacting proteins. We show that Hace1 interacts with cullin-associated NEDD8-dissociated protein 1 (CAND1) under nutrient depletion and hypoxia. CAND1 binds cullins and prevents their entry into cullin ring E3 ligase (CRL) complexes, thus blocking CRL activity. Hace1 binding releases CUL1/2 from CAND1, facilitating assembly of CRL complexes to degrade cyclin D1 and HIF1alpha, respectively. These findings suggest a br

ORGANISM(S): Homo sapiens

SUBMITTER: Tony Ng 

PROVIDER: E-GEOD-25452 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress