Zinc-finger protein p52-ZER6 accelerates colorectal cancer cell proliferation and tumour progression through promoting p53 ubiquitination.

摘要: Abstract Background Aberrant expression of p53 and its downstream gene p21 is closely related to alterations in cell cycle proliferation, common among cancer patients. However, the underlying molecular mechanism has not been fully unravelled. ZER6 a zinc-finger protein with two isoforms possessing different amino termini (N-termini) their proteins, p52-ZER6 p71-ZER6. The biological function isoforms, as well potential involvement tumourigenesis regulation remain elusive. Methods effect on was determined using specific knockdown overexpression. tumours analysed clinical specimens, while modulation used explore roles regulating proliferation tumourigenesis. p53/p21 axis studied biology biochemical methods. Findings highly expressed tumour tissues, progression. Mechanistically, bound through truncated KRAB (tKRAB) domain N-terminus enhanced MDM2/p53 complex integrity, leading increased ubiquitination degradation. p52-ZER6-silencing induced G0-G1 phase arrest, subsequently reduced Intriguingly, this p52-ZER6, whereas p71-ZER6 did affect stability, most likely due presence HUB-1 domain. Interpretation We identified novel oncogene that enhances might be target for anti-cancer therapy.