PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6

Abstract

HOXB9 is a homeobox domain-containing transcription factor, playing an important role in embryonic development and cancer progression. However, the precise post-translational modifications (PTMs) of HOXB9 and the corresponding roles are unclear. Here, we report that acetyltransferase p300/CBP-associated factor (PCAF) interacts with and acetylates HOXB9 both in vivo and in vitro. Conversely, the acetylation of HOXB9 can be reversed by deacetylase SIRT1. Furthermore, we found that HOXB9 is acetylated at lysine 27 (AcK27). Functionally, in contrast to the wild type HOXB9, AcK27-HOXB9 decreased its capacity in promoting lung cancer cell migration and tumor growth in mice. Mechanistically, AcK27-HOXB9 suppresses the transcription of its target gene Jumonji domain-containing protein 6 (JMJD6) by direct occupying the promoter of JMJD6 gene. For clinical relevance, elevated HOXB9 acetylation at K27 predicts a better prognosis in lung adenocarcinoma patients. Taken together, we identified the first PTM of HOXB9 by demonstrating that HOXB9 can be acetylated and AcK27-HOXB9 counteracts the role of the wild-type HOXB9 in regulating lung adenocarcinoma progression.

The role of phosphatidylserine recognition receptors in multiple biological functions

“…In fact, homomultimers of PSR may function as scaffolding nuclear proteins with histone arginine demethylase activity regulating gene expression [172][173][174][175][176][177][178]. The upregulation of PSR has been described as an oncogenic driver in some tumor types [175,176,179,180].…”

Kindlin-2 Inhibits the Hippo Signaling Pathway by Promoting Degradation of MOB1

“…Immunoprecipitation methods were described previously (Wan et al, 2016). In brief, RIPA buffer (1 3 PBS, pH 7.4, 0.5% sodium deoxycholate, 1% Triton X-100, and 0.1% SDS) with protease inhibitor cocktail was used to treat 293A, HKC, or HK2 cell lysates, and then cell debris was removed through centrifugation at 12,000 rpm for 10 minutes.…”

Differential Effects of Histone Acetyltransferase GCN5 or PCAF Knockdown on Urothelial Carcinoma Cells

“…In various cancers, GCN5 acts in a rather oncogenic fashion [ 9 , 10 , 11 , 12 ], which is usually ascribed to its function as a coactivator of the c-MYC (V-Myc Avian Myelocytomatosis Viral Oncogene Homolog) oncogene protein [ 13 , 14 , 15 ]. For PCAF, both pro- and anti-tumorigenic properties have been observed in different cancer types [ 16 , 17 , 18 , 19 , 20 , 21 ]. Specifically, PCAF regulates MDM2 (Mouse Double Minute 2) stability and function, and vice versa [ 22 , 23 , 24 ].…”