KAP1/TRIM28: Transcriptional Activator and/or Repressor of Viral and Cellular Programs?

Several transcriptional and epigenetic regulators have been functionally linked to the control of viral and cellular gene expression programs. One such regulator is Kruppel-associated box (KRAB)-associated protein 1 (KAP1: also named TRIM28 or TIF1 beta), which has been extensively studied in the past three decades. Here we offer an up-to date review of its various functions in a diversity of contexts. We first summarize the discovery of KAP1 repression of endogenous retroviruses during development. We then deliberate evidence in the literature suggesting KAP1 is both an activator and repressor of HIV-1 transcription and discuss experimental differences and limitations of previous studies. Finally, we discuss KAP1 regulation of DNA and RNA viruses, and then expand on KAP1 control of cellular responses and immune functions. While KAP1 positive and negative regulation of viral and cellular transcriptional programs is vastly documented, our mechanistic understanding remains narrow. We thus propose that precision genetic tools to reveal direct KAP1 functions in gene regulation will be required to not only illuminate new biology but also provide the foundation to translate the basic discoveries from the bench to the clinics.

Automated summary

This article provides an up-to-date review of the various functions of KAP1 in different contexts, including its repression of endogenous retroviruses, its role as both an activator and repressor of HIV-1 transcription, its regulation of DNA and RNA viruses, and its control of cellular responses and immune functions. Despite the extensive research on KAP1's positive and negative regulation of viral and cellular transcriptional programs, our understanding of its mechanisms remains limited.