Sub1, also known as the transcriptional coactivator PC4 in humans, is a DNA-binding protein with multiple functions. It was initially identified as a co-activator during transcription initiation. It is involved in mRNA biogenesis processes such as elongation, termination, and RNAPII phosphorylation, and also participates in RNAPIII transcription. Sub1 has been associated with maintaining genome stability and is involved in DNA-dependent processes like replication and DNA repair [1,3,4].

In atherosclerotic mice models, transgenic myeloid-specific Sub1 knockout in ApoE-/-mice showed that Sub1 mediates the pro-atherosclerotic effects of TLR2 and TLR4 signaling. Sub1 knockout in macrophages enhanced anti-inflammatory M2 macrophage polarization and cholesterol efflux, and irradiated Ldlr-/-mice transplanted with Sub1-/-murine bone marrow displayed reduced atherosclerosis. Promoter analysis revealed Sub1-dependent activation of Irf1 transcription in a Ck2-dependent manner, and Sub1-knockout macrophages had decreased Irf1 expression [5]. In colorectal cancer, depletion of SUB1 in vitro and in vivo inhibited the invasive and metastatic abilities of CRC cells. SUB1 activated NF-κB signaling by modulating UBR5-mediated ubiquitination of UBXN1, driving CRC metastasis [2].

In conclusion, Sub1 is a multifaceted factor involved in transcription and genome stability. Studies using knockout mouse models have revealed its role in diseases like atherosclerosis and colorectal cancer. These models help in understanding how Sub1 contributes to disease-related biological processes, potentially providing new therapeutic targets for these diseases.