Nemo-Like Kinase (NLK) Primes Colorectal Cancer Progression by Releasing the E2F1 Complex from HDAC1

Control of E2F1 activity is restricted via its interactions with RB1 and HDAC1. However, the detailed regulatory mechanisms underlying the E2F1/HDAC1 complex remain elusive. Here, we report that nemo-like kinase (NLK) boosts cell cycle progression, which facilitates tumor development by releasing the E2F1 protein from HDAC1. Deletion of NLK largely blocks colorectal tumor proliferation and development. Moreover, RNA-seq shows that cell cycle is arrested at the G1/S phase in NLK-deficient cells and that the expression of E2F complex-targeted genes is affected, whereas overexpression of NLK but not an NLK mutant restores the wild-type phenotype.
Source: Cancer Letters - Category: Cancer & Oncology Authors: Tags: Original Articles Source Type: research