A CK2 and SUMO-dependent, PML NB-involved regulatory mechanism controlling BLM ubiquitination and G-quadruplex resolution.
Shichang LiuErin AtkinsonAdriana Paulucci-HolthauzenBin WangPublished in: Nature communications (2023)
The Boom syndrome helicase (BLM) unwinds a variety of DNA structures such as Guanine (G)-quadruplex. Here we reveal a role of RNF111/Arkadia and its paralog ARKL1, as well as Promyelocytic Leukemia Nuclear Bodies (PML NBs), in the regulation of ubiquitination and control of BLM protein levels. RNF111 exhibits a non-canonical SUMO targeted E3 ligase (STUBL) activity targeting BLM ubiquitination in PML NBs. ARKL1 promotes RNF111 localization to PML NBs through SUMO-interacting motif (SIM) interaction with SUMOylated RNF111, which is regulated by casein kinase 2 (CK2) phosphorylation of ARKL1 at a serine residue near the ARKL1 SIM domain. Upregulated BLM in ARKL1 or RNF111-deficient cells leads to a decrease of G-quadruplex levels in the nucleus. These results demonstrate that a CK2- and RNF111-ARKL1-dependent regulation of BLM in PML NBs plays a critical role in controlling BLM protein levels for the regulation of G-quadruplex.
Keyphrases
- protein kinase
- dna damage response
- cancer therapy
- single molecule
- amino acid
- acute myeloid leukemia
- transcription factor
- protein protein
- bone marrow
- high resolution
- oxidative stress
- small molecule
- genome wide
- case report
- binding protein
- drug delivery
- cell cycle arrest
- cell proliferation
- tyrosine kinase
- cell free
- dna damage
- dna repair