Fig. 8
From: Liquid–liquid phase separation in human health and diseases
LLPS in cancer. a Speckle-type POZ protein (SPOP) can phase-separate with its substrates and cullin3-RING ubiquitin ligase to form condensates, which promote the degradation of its substrates via the ubiquitin-proteasome system. SPOP consists of a substrate-binding meprin and TRAF homology (MATH) domain and two dimerization domains, BTB and BACK. The self-association by two dimerization domains and the multievent interactions between MATH domain and substrates are necessary for the phase separation of SPOP. Cancer-associated mutations in the MATH domain disrupt the formation of SPOP condensate by preventing the interaction between substrates and SPOP. b The transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) can activate the transcription of various genes via LLPS. The Hippo signaling pathway can inhibit the formation of YAP/TAZ condensates. However, the Hippo signaling pathway is inactivated in many cancers. Therefore, the accumulation of TAZ and YAP can largely activate the transcription of proto-oncogenes via phase separation, promoting cell proliferation and anti-PD-1 immunotherapy resistance via LLPS. The intrinsically disordered TA and CC domains are essential for the formation of YAP condensates, whereas the CC and WW domains are vital for TAZ phase separation
