Wellcome Centre for Cell-Matrix Research

Tracking CDK1 Dynamics With a Novel Biosensor Mouse and Clinical Cohorts to Predict CDK4/6 Inhibitor Sensitivity in ER+ Breast Cancer

ABSTRACT High‐risk estrogen receptor positive (ER+) early breast cancer (EBC) is managed with endocrine therapies and cyclin‐dependent kinase (CDK) 4/6 inhibitors, although no standard molecular markers clinically identify these tumors. CDK1 lies immediately downstream of CDK4/6...

Targeting biglycan–TLR2/TLR4 interaction with synthetic peptides mitigates inflammation and ameliorates renal function in ischemia–reperfusion injury

Renal ischemia–reperfusion injury (IRI), characterized by enhanced inflammation, is a leading cause of acute kidney injury (AKI) with limited treatments beyond supportive dialysis. Biglycan through toll-like receptors (TLR)2/TLR4 signaling aggravates tissue damage in acute renal...

FAF1 and FAF2 enhance unfolding by p97-UFD1-NPL4 complex enabling rational design of p97 activators

Abstract VCP/p97 is an AAA+ ATPase that, together with its cofactors UFD1-NPL4 (p97-UN), unfolds ubiquitylated substrates to maintain cellular homeostasis. The human p97-UN complex associates with additional cofactors, but how these cofactors modulate p97-UN activity is not fully...