RESUMEN
Programmed death ligand-1 (PD-L1) is a key component of tumor immunosuppression. The uneven therapeutic results of PD-L1 therapy have stimulated intensive studies to better understand the mechanisms underlying altered PD-L1 expression in cancer cells, and to determine whether, beyond its immune function, PD-L1 might have intracellular functions promoting tumor progression and resistance to treatments. In this Opinion, we focus on paradigmatic examples highlighting the central role of PD-L1 in post-transcriptional regulation, with PD-L1 being both a target and an effector of molecular mechanisms featured prominently in RNA research, such as RNA methylation, phase separation and RNA G-quadruplex structures, in order to highlight vulnerabilities on which future anti-PD-L1 therapies could be built.
Asunto(s)
Antígeno B7-H1 , Neoplasias , ARN , Humanos , Antígeno B7-H1/metabolismo , ARN/metabolismo , ARN/genética , Animales , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/inmunología , Tolerancia Inmunológica , Terapia de Inmunosupresión , Procesamiento Postranscripcional del ARN , Regulación Neoplásica de la Expresión Génica , G-CuádruplexRESUMEN
Eukaryotic genomes are folded into DNA loops mediated by structural maintenance of chromosomes (SMC) complexes such as cohesin, condensin, and Smc5/6. This organization regulates different DNA-related processes along the cell cycle, such as transcription, recombination, segregation, and DNA repair. During the G2 stage, SMC-mediated DNA loops coexist with cohesin complexes involved in sister chromatid cohesion (SCC). However, the articulation between the establishment of SCC and the formation of SMC-mediated DNA loops along the chromatin remains unknown. Here, we show that SCC is indeed a barrier to cohesin-mediated DNA loop expansion along G2/M Saccharomyces cerevisiae chromosomes.
