Functions and mechanisms of lysine crotonylation

Abstract

Lysine crotonylation is a newly discovered post-translational modification, which is structurally and functionally different from the widely studied lysine acetylation. Recent advances in the identification and quantification of lysine crotonylation by mass spectrometry have revealed that non-histone proteins are frequently crotonylated, implicating it in many biological processes through the regulation of chromatin remodelling, metabolism, cell cycle and cellular organization. In this review, we summarize the writers, erasers and readers of lysine crotonylation, and their physiological functions, including gene transcription, acute kidney injury, spermatogenesis, depression, telomere maintenance, HIV latency and cancer process. These findings not only point to the new functions for lysine crotonylation, but also highlight the mechanisms by which crotonylation regulates various cellular processes.

Keywords: HCT; HDCR; PTM; crotonylation; reader.

Figure 1

Illustrations of histone crotonylation sites in human. All reported lysine (K) crotonylation sites on histone H1, H2A, H2B, H3 and H4 are shown in different colours

Figure 2

Protein crotonylation is balanced by HCT and HDCR, and recruits Readers. Protein crotonylation can be enzymatically catalysed by lysine crotonyltransferase (HCT) and removed by decrotonylase (HDCR). Crotonylations can also act as docking marks to recruit downstream readers