Insights into Noncanonical and Diversified Functions of ABCF1: From Health to Disease

Abstract

The ATP-binding cassette (ABC) family is one of the largest and most ancient classes of transporters found in nearly all living organisms. However, ABCF1 lacks a transmembrane domain and therefore does not function as a transporter. Recent studies point to an unexpectedly diverse role of ABCF1 in regulating cell-essential processes from mRNA translation, innate immune response, and phagocytosis in somatic cells, to transcriptional regulation in embryonic stem cells. ABCF1's functional plasticity is in part mediated by its disordered low-complexity domain (LCD) to enable dynamic biomolecular interactions. In this review, we discuss how ABCF1 takes advantage of the LCD to expand its functional repertoire and highlight fundamental principles of biomolecular assembly driving biological reactions. We also discuss the functions and mechanisms of ABCF1 in development and tissue homeostasis, and how dysregulation of ABCF1 contributes to diseases such as inflammatory disease and cancer.

Keywords: innate immune sensors; low-complexity domain; phase separation; transcription; translation.