Molecular basis for nuclear accumulation and targeting of the inhibitor of apoptosis BIRC2.

ABSTRACT: The inhibitor of apoptosis protein BIRC2 regulates fundamental cell death and survival signaling pathways. Here we show that BIRC2 accumulates in the nucleus via binding of its second and third BIR domains, BIRC2_BIR2 and BIRC2_BIR3, to the histone H3 tail and report the structure of the BIRC2_BIR3-H3 complex. RNA-seq analysis reveals that the genes involved in interferon and defense response signaling and cell-cycle regulation are most affected by depletion of BIRC2. Overexpression of BIRC2 delays DNA damage repair and recovery of the cell-cycle progression. We describe the structural mechanism for targeting of BIRC2_BIR3 by a potent but biochemically uncharacterized small molecule inhibitor LCL161 and demonstrate that LCL161 disrupts the associatio

SUBMITTER: Tencer AH 

PROVIDER: S-EPMC10702411 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature