SIRT7 Orchestrates Ligand‐Dependent ERα Signaling Rewiring to Drive Tamoxifen Resistance in ERα‐positive Breast Cancer In tamoxifen-sensitive breast cancer, SIRT7 deacetylates ERα at lysines 302 and 303, promoting CHIP-mediated, ubiquitin-dependent proteasomal degradation of ERα and thereby restraining estrogen-drive...

#Article in #MedComm_Oncology

Researchers from HunanUniversity find that #SIRT7 Orchestrates Ligand-Dependent ERα Signaling Rewiring to Drive #Tamoxifen Resistance in #ERα-positive #BreastCancer doi.org/10.1002/mog2...

#Deacetylation #DrugResistance

By comparing structures trapped at each substrate position we could rationalize its activity and intrinsic selectivity 🔍.
#SIRT7 binding is optimal for targeting #H3K36ac, and it can only access #H3K18ac through partial disengagement from the nucleosome and DNA bending.
(4/8)

Babatunde Ekundayo generated beautiful high-resolution structures, where we identified:
- A unique N-terminal nucleosome-binding domain, which places the #SIRT7 catalytic domain by the H3 tail exit site
- Extensive contacts with the two DNA gyres!
(3/8)

#SIRT7 is a histone deacetylase with highly specific activity on #chromatin substrates.
We just published mechanism-based #cryoEM structures of #SIRT7 on nucleosomes to understand its activity 👇
www.nature.com/articles/s41...
(1/8) #ChemBio #ChemSky

#SIRT7 protects against VitD3-induced🐭#VascularCalcification

SIRT7 does Not directly modify osteogenic factors RUNX2/BMP2 or contractile markers in 🐭aortic #SmoothMuscleCell +high Pi
Instead, SIRT7 appears antioxidant & anti-senescent

#FreeRadicBiolMed 2024
www.sciencedirect.com/science/arti...