C6orf89 encodes three distinct HDAC enhancers that function in the nucleolus, the golgi and the midbody

Abstract

We report here that C6orf89, which encodes a protein that interacts with bombesin receptor subtype‐3 and accelerates cell cycle progression and wound repair in human bronchial epithelial cells (Liu et al., 2011, PLoS ONE 6: e23072), encodes one soluble and two type II membrane proteins that function as histone deacetylases (HDAC) enhancers. Soluble 34/64sp is selectively targeted to the nucleolus and is retained in nucleolar organiser regions (NORs) in mitotic cells. Nucleolar 34/64sp is integrated into the ribosomal gene transcription machinery, colocalises and coimmunoprecipitates with the Pol I transcription factor UBF, and undergoes a dramatic relocalisation to the nucleolus upon the arrest of rDNA transcription, protein synthesis and PI3K/mTORC2 signalling. Membrane 42/116mp localises to the Golgi and the midbody, and its controlled ectopic expression provokes the disruption of the Golgi cisternae and hinders the separation of daughter cells and the completion of mitosis. The latter effect is also produced by the microinjection of an affinity‐purified amfion antibody. The identification of C60rf89 as a gene that encodes three distinct proteins with the capacity to enhance the activity of histone deacetylases (HDACs) in the nucleolus, the Golgi and the midbody provides new information regarding the components of the acetylome and their capacity to interact with different functional groups in the cell. J. Cell. Physiol. 228: 1907–1921, 2013. © 2013 Wiley Periodicals, Inc.

Bombesin Receptor‐Activated Protein (BRAP) Modulates NF‐κB Activation in Bronchial Epithelial Cells by Enhancing HDAC Activity

“…BRAP contains 354 amino acids and was reported to be a type II membrane protein with a possible N‐terminal transmembrane (TM) domain [Lalioti et al, ]. All three of the proteins encoded by C6ORF89 , including BRAP, have been shown to be capable of enhancing histone deacetylase (HDAC) activity in Vero cells [Lalioti et al, ]. In an attempt to induce airway hyperresponsiveness in mice via oxidative stress, we found that the expression level of BRAP was significantly up‐regulated in the lung epithelia of mice after ozone exposure.…”

“…Functional analysis revealed that this protein might accelerate cell cycle progression and wound repair in HBECs [Liu et al, ]. BRAP is one of the three proteins encoded by the C6ORF89 gene as characterized by Lalioti et al []. BRAP contains 354 amino acids and was reported to be a type II membrane protein with a possible N‐terminal transmembrane (TM) domain [Lalioti et al, ].…”

“…BRAP is one of the three proteins encoded by the C6ORF89 gene as characterized by Lalioti et al []. BRAP contains 354 amino acids and was reported to be a type II membrane protein with a possible N‐terminal transmembrane (TM) domain [Lalioti et al, ]. All three of the proteins encoded by C6ORF89 , including BRAP, have been shown to be capable of enhancing histone deacetylase (HDAC) activity in Vero cells [Lalioti et al, ].…”

The Endoplasmic Reticulum-based Acetyltransferases, ATase1 and ATase2, Associate with the Oligosaccharyltransferase to Acetylate Correctly Folded Polypeptides

“…Interestingly enough, as with the UDPglucose:glycoprotein glucosyltransferase/calnexin system, N ⑀ -lysine acetylation is also a transient event. In fact, the acetyl group is removed once the protein reaches the Golgi apparatus by a Golgibased deacetylase (2), probably amfion/C6orf89, a recently identified deacetylase that resides in the cis-Golgi (32). Although N ⑀ -lysine acetylation shares some similarities with the UDP-glucose: glycoprotein glucosyltransferase/calnexin system, it differs in the fact that it "marks" correctly folded and not unfolded/misfolded polypeptides.…”

Nε-lysine acetylation in the endoplasmic reticulum – a novel cellular mechanism that regulates proteostasis and autophagy

“…This has been a standing question since the observation that BACE1 is acetylated in the ER and deacetylated in the Golgi as it transits through the secretory pathway (Costantini et al, 2007). Interestingly, an isoform of the Bombesin receptor-activated protein (the protein product of C6orf89), which localizes to the cis-Golgi and Golgi cisternae and possess deacetylase enhancer activity has been identified (Lalioti et al, 2013). Whether C6orf89 is the actual deacetylase or just an enhancer, as suggested, remains to be fully determined.…”