Fragile-site associated tumor suppressor (FATS) (FATS)

Fragile-site associated tumor suppressor (FATS), encoded by the C10orf90 gene, is a multifunctional protein characterized primarily by its role as a tumor suppressor and cell cycle regulator[1][7]. It sustains the G2/M checkpoint following DNA damage by acting as a p53 activator: FATS inhibits the interaction of MDM2 with p53, promotes p53 non-proteolytic polyubiquitination, and enhances p53-dependent transcription of cell cycle regulator CDKN1A/p21—a process vital for robust DNA damage response and cell cycle arrest[1][7]. FATS has E3 ubiquitin ligase activity that assembles ubiquitin polymers independently of traditional E2-conjugating enzymes, and also mediates the stability of CDKN1A/p21 in a ubiquitin-independent manner. The protein localizes to the centrosome and is implicated in primary cilium assembly, cell cycle process regulation, and response to ionizing radiation[2][3][4]. Deficiency or mutation of C10orf90/FATS is associated with tumorigenesis and genetic syndromes such as 10q26 deletion syndrome and 3-methylglutaconic aciduria with neurological involvement[1].

Other names

Chromosome 10 open reading frame 90C10orf90FLJ32938bA422P15.2centrosomal protein C10orf90E2/E3 hybrid ubiquitin-protein ligase FATSfragile-site associated tumor suppressor homolog

Activation of p53 via inhibition of MDM2 binding and non-proteolytic polyubiquitination of p53; Promotion of CDKN1A/p21 stability and acetylation via interaction with HDAC1