Cell density-dependent acetylation of ΔNp63α is associated with p53-dependent cell cycle arrest

Chae, Yang-Seok,Kim, Hyunji,Kim, Dongsung,Lee, Hyunsook,Lee, Hae-ock Elsevier 2012 FEBS letters Vol.586 No.8

<P><B>Highlights</B></P><P>► Acetylation regulates the function of p53 family members. ► We identified acetylation sites for p63 and generated acetyl-p63 specific antibodies. ► Acetylation of ΔNp63α is associated with cell cycle arrest in high density cell culture. ► Acetylation of ΔNp63α may be a mechanism for epidermal homeostasis.</P> <P><B>Abstract</B></P><P>ΔNp63α is a p63 isoform that is predominantly expressed in the epidermal stem cells and in cancer. To find the regulatory pathways of ΔNp63α, we assessed whether ΔNp63α is acetylated and determined the functional implications of acetylation. First, the hinge region of p63 was shown to be acetylated by PCAF, similarly to other p53 family members. Second, acetylation synergistically induced cytoplasmic localization of ΔNp63α. Finally, acetyl-ΔNp63α was induced during high-density culture, suggesting that acetylation of ΔNp63α may reinforce cell cycle arrest upon cell contact. Altogether, these findings suggest that acetylation of ΔNp63α contributes to the epidermal homeostasis.</P><P><B>Structured summary of protein interactions</B></P><P><B>PCAF</B> acetylates <B>ΔNp63α</B> by acetylation assay (View Interaction: <U>1</U>, <U>2</U>, <U>3</U>)</P><P><B>ΔNp63α</B> physically interacts with <B>ΔNp63α</B> by anti tag coimmunoprecipitation (<U>View interaction</U>)</P><P><B>ΔNp63α</B> physically interacts with <B>p53</B> by anti bait coimmunoprecipitation (<U>View interaction</U>)</P>

Regulation of UHRF1 acetylation by TIP60 is important for colon cancer cell proliferation

Hong Ye Joo,Park Junyoung,Hahm Ja Young,Kim Song Hyun,Lee Dong Ho,Park Kwon-Sik,Seo Sang-Beom 한국유전학회 2022 Genes & Genomics Vol.44 No.11

Background: Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is upregulated in colon cancer cells and associated with silencing tumor suppressor genes (TSGs) to promote colon cancer cell proliferation. Objective: To investigate epigenetic modification of UHRF1 by TIP60. Whether UHRF1 acetylation by TIP60 can induce cell proliferation in colon cancer cells. Methods: Acetylation sites of UHRF1 by TIP60 was predicted by ASEB (Acetylation Set Enrichment Based) method and identified by immunoprecipitation assay using anti-pan-acetyl lysine antibody and in vitro acetylation assay. Based on this method, UHRF1 acetylation-deficient mimic 4KR (K644R, K646R, K648R, K650R) mutant was generated to investigate effects of UHRF1 acetylation by TIP60. shRNA system was used to generate stable knockdown cell line of UHRF1. With transient transfection of UHRF1 WT and 4KR, the effects of UHRF1 4KR mutant on Jun dimerization protein 2 (JDP2) gene expression, cell proliferation and cell cycle were investigated by RT-qPCR and FACS analysis in shUHRF1 colon cancer cell line. Results: Downregulation of TIP60-mediated UHRF1 acetylation is correlated with suppressed cell cycle progression. Acetylation-deficient mimic of UHRF1 showed poor cell growth through increased expression of JDP2 gene. Conclusions: Acetylation of UHRF1 4K residues by TIP60 is important for colon cancer cell growth. Furthermore, upregulated JDP2 expression by acetylation-deficient mutant of UHRF1 might be an important epigenetic target for colon cancer cell proliferation.

The separation of alginate biosynthesis and acetylation in Pseudomonas syringae

Lee, Jin W.,Day, F. 東亞大學校附設遺傳工學硏究所 1999 遺傳工學硏究 Vol.- No.6

Seaweed alginate was acetylated by resting cells of Pseudomonas syringae subsp.phaseolicola ATCC 19304. Physiological studies on this strain and its UV-induced mutants showed no correlation between bacterial alginate biosynthesis and acetylation. Specific yields of alginate and degree of acetylation in these polymers varied with strain and culture medium. This was indirect evidence that alginate bioshynthesis is separate from polysaccharide acetylation. It indicated that the enzyme system involved in alginate biosynthesis was not directly linked to alginate acetylation and explained why microbial acetylation of seaweed alginates was possible. L'alginate d'algues marines est acetyle par des cellules au repos du Pseudomonas syringae shbsp.phaseolicola ATCC 19304. Des etudes physiologiques sur cette souche et ses mutants induits par UV n'ont pas montre de correlation entre la biosynthese bacterienne d'alginate et l'acetylation. Les rendements specifiques d'alginate et le degre d'acetylation chez ces polymeres variaient selon la souche et le milieu de culture. Cela prouve indirectement que la biosynthese d'alginate est distincte de l'acetylation des polysaccharides. Cela indique que le systeme enzymatique implique dans la biosynthese de l'alginate n'est pas directement lie a l'acetylation de l'alginate et explique pourquoi l'acetylation microbienne des alginates d'algues est possible.

Regulation of Acetylation of Histone Deacetylase 2 by p300/CBP-Associated Factor/Histone Deacetylase 5 in the Development of Cardiac Hypertrophy

Eom, Gwang Hyeon,Nam, Yoon Seok,Oh, Jae Gyun,Choe, Nakwon,Min, Hyun-Ki,Yoo, Eun-Kyung,Kang, Gaeun,Nguyen, Vu Hong,Min, Jung-Joon,Kim, Jong-Keun,Lee, In-Kyu,Bassel-Duby, Rhonda,Olson, Eric N.,Park, Woo Grune & Stratton 2014 Circulation research Vol.114 No.7

<P><B><U>Rationale:</U></B></P><P>Histone deacetylases (HDACs) are closely involved in cardiac reprogramming. Although the functional roles of class I and class IIa HDACs are well established, the significance of interclass crosstalk in the development of cardiac hypertrophy remains unclear.</P><P><B><U>Objective:</U></B></P><P>Recently, we suggested that casein kinase 2α1–dependent phosphorylation of HDAC2 leads to enzymatic activation, which in turn induces cardiac hypertrophy. Here we report an alternative post-translational activation mechanism of HDAC2 that involves acetylation of HDAC2 mediated by p300/CBP-associated factor/HDAC5.</P><P><B><U>Methods and Results:</U></B></P><P>Hdac2 was acetylated in response to hypertrophic stresses in both cardiomyocytes and a mouse model. Acetylation was reduced by a histone acetyltransferase inhibitor but was increased by a nonspecific HDAC inhibitor. The enzymatic activity of Hdac2 was positively correlated with its acetylation status. p300/CBP-associated factor bound to Hdac2 and induced acetylation. The HDAC2 K75 residue was responsible for hypertrophic stress–induced acetylation. The acetylation-resistant Hdac2 K75R showed a significant decrease in phosphorylation on S394, which led to the loss of intrinsic activity. Hdac5, one of class IIa HDACs, directly deacetylated Hdac2. Acetylation of Hdac2 was increased in Hdac5-null mice. When an acetylation-mimicking mutant of Hdac2 was infected into cardiomyocytes, the antihypertrophic effect of either nuclear tethering of Hdac5 with leptomycin B or Hdac5 overexpression was reduced.</P><P><B><U>Conclusions:</U></B></P><P>Taken together, our results suggest a novel mechanism by which the balance of HDAC2 acetylation is regulated by p300/CBP-associated factor and HDAC5 in the development of cardiac hypertrophy.</P>

Alterations of the degree of xylan acetylation in Arabidopsis xylan mutants.

Lee, Chanhui,Teng, Quincy,Zhong, Ruiqin,Ye, Zheng-Hua Landes Bioscience 2014 Plant signaling & behavior Vol.9 No.2

<P>Xylan is the second most abundant polysaccharide in secondary walls of dicot plants and one of its structural features is the high degree of acetylation of xylosyl residues. In Arabidopsis, about 60% of xylosyl residues in xylan are acetylated and the biochemical mechanisms controlling xylan acetylation are largely unknown. A recent report by Yuan et al. (2013) revealed the essential role of a DUF231 domain-containing protein, ESKIMO1 (ESK1), in xylan acetylation in Arabidopsis as the esk1 mutation caused specific reductions in the degree of xylan 2-O or 3-O-monoacetylation and in the activity of xylan acetyltransferase. Interestingly, the esk1 mutation also resulted in an elevation of glucuronic acid (GlcA) substitutions in xylan. Since GlcA substitutions in xylan occur at the O-2 position of xylosyl residues, it is plausible that the increase in GlcA substitutions in the esk1 mutant is attributed to the reduction in acetylation at O-2 of xylosyl residues, which renders more O-2 positions available for GlcA substitutions. Here, we investigated the effect of removal of GlcA substitutions on the degree of xylan acetylation. We found that a complete loss of GlcA substitutions in the xylan of the gux1/2/3 triple mutant led to a significant increase in the degree of xylan acetylation, indicating that xylan acetyltransferases and glucuronyltransferases compete with each other for xylosyl residues for their acetylation or GlcA substitutions in planta. In addition, detailed structure analysis of xylan from the rwa1/2/3/4 quadruple mutant revealed that it had a uniform reduction of acetyl substitutions at different positions of the xylosyl residues, which is consistent with the proposed role of RWAs as acetyl coenzyme A transporters. The significance of these findings is discussed.</P>

Acetylation of Retinoblastoma Like Protein2 (Rb2/p130) in Tumor Tissues

Khan, Z.N.,Sabir, M.,Kayani, M.A.,Saeed, M. Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

The activity of Rb proteins is controlled by post-translational modifications, especially through phosphorylation. Acetylation of Rb2/p130 was reported recently in NIH3T3 cells but its physiological relevance in cell cycle control and tumorigenesis is still unknown. Efforts are underway to investigate possible interplay between Rb2/p130 phosphorylation and acetylation. Here we hypothesized that Rb2/p130 acetylation, like p53 acetylation, may play a role in development of the tumor phenotype. The proposed hypothesis regarding acetylation of Rb2/p130 in tumor VS normal cells was found to be true in our case study of 36 tumor samples. Statistical analysis of results suggest strong correlation among Rb2/p130 acetylation and cancer phenotype.

Yellowing Inhibition of Bagasse Chemimechanical Pulp

ALI ABDULKHANI,SEYED AHMAD MIRSHOKRAIE,AHMAD JAHAN LATIBARI,ALI AKBAR ENAYATI 한국펄프·종이공학회 2006 한국펄프종이학회 기타 간행물 Vol.- No.-

Papers made from unbleached and bleached bagasse chemimechanical pulp were chemically modified by acetylation. The effects of irradiation on unbleached and bleached also reduced papers of bagasse chemimechanical pulp before and after acetylation were investigated in this study. Chemimechanical pulp was prepared from bagasse and then bleached with hydrogen peroxide. Unbleached and hydrogen bleached pulps were reduced by Sodium borohydride in different procedures. Paper sheets were prepared from pulps and then acetylated using a technical grade of acetic anhydride. Accelerated photo-aging was run on the samples using fluorescent lamps to verify photo-stability of paper sheets before and after pretreatments. Brightness reversion (as Post-color number) and other optical properties of the paper sheets were measured. Efficient inhibition of photo-yellowing of papers made from bagasse CMP was achieved by acetylation. The acetylated unbleached CMP was noticeably photo-bleached during irradiation. Sodium borohydride reduction followed by acetylation had the same effect as acetylation alone at the same degree of reaction time and reductive treatment did not affect the yellowing rate to any great extent. The pre-reduced, acetylated unbleached papers were, however, not brightened during irradiation. Calculation done by Kubelka-Munk equation showed that reductive treatment had little effect in reducing the photo-yellowing of paper made from CMP pulp; a small stabilization effect was observed in the case of bleached CMP, while unbleached CMP was slightly more prone to discolor in the later phase of photo-reversion. The improved stability towards light may was closely related to the decrease in the phenolic hydroxyl content as a result of blocking by acetyl groups during treatment with acetic anhydride. The results support the hypothesis that phenolic hydroxyl has an important role in the process of photo-reversion of high-yield pulps. The results obtained in this study demonstrate that the acetylation of paper manufactured from peroxide bleached Bagasse CMP significantly retards light-induced discoloration. The inhibition of yellowing is connected with a decrease in the phenolic hydroxyl content of both unbleached and peroxide bleached papers.

BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis

Choi, Eunhee,Choe, Hyerim,Min, Jaewon,Choi, Ji Yoon,Kim, Jimi,Lee, Hyunsook Nature Publishing Group 2009 The EMBO journal Vol.28 No.14

<P>Regulation of BubR1 is central to the control of APC/C activity. We have found that BubR1 forms a complex with PCAF and is acetylated at lysine 250. Using mass spectrometry and acetylated BubR1-specific antibodies, we have confirmed that BubR1 acetylation occurs at prometaphase. Importantly, BubR1 acetylation was required for checkpoint function, through the inhibition of ubiquitin-dependent BubR1 degradation. BubR1 degradation began before the onset of anaphase. It was noted that the pre-anaphase degradation was regulated by BubR1 acetylation. Degradation of an acetylation-mimetic form, BubR1–K250Q, was inhibited and chromosome segregation in cells expressing BubR1–K250Q was markedly delayed. By contrast, the acetylation-deficient mutant, BubR1–K250R, was unstable, and mitosis was accelerated in BubR1–K250R-expressing cells. Furthermore, we found that APC/C–Cdc20 was responsible for BubR1 degradation during mitosis. On the basis of our collective results, we propose that the acetylation status of BubR1 is a molecular switch that converts BubR1 from an inhibitor to a substrate of the APC/C complex, thus providing an efficient way to modulate APC/C activity and mitotic timing.</P>

Effect of Low Level of Starch Acetylation on Physicochemical Properties of Potato Starch

Hetti Arachchige Mangalika Wic,Kazuo Yamamoto,Hiroaki Yamauchi,Takahiro Noda 한국식품과학회 2009 Food Science and Biotechnology Vol.18 No.1

In order to find out the effect of low level of starch acetylation on physicochemical properties of potato starch, amylose content, digestibility of raw and gelatinized starch, thermal properties, pasting properties, and the swelling power of native and acetylated potato starches were measured. The amylose content was significantly lower in acetylated starch than in their counterpart native starches. Though a tendency in the decrease in digestibility of raw starch was observed with starch acetylation, acetylation did not alter the proportion of readily digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS) of both raw and gelatinized potato starches. No clear increase in the swelling power was observed, however, the peak and onset gelatinization temperatures and the enthalpy required for starch gelatinization decreased with starch acetylation. Peak and breakdown viscosities were reduced due to acetylation of potato starch while final viscosity and set back were increased.

Histone Acetylation Level and Histone Acetyltransferase/Deacetylase Activity in Ejaculated Sperm from Normozoospermic Men

김지현,지병철,이장미,서창석,김석현 연세대학교의과대학 2014 Yonsei medical journal Vol.55 No.5

Purpose: The aim of this work was to evaluate nuclear histone acetylation level and total histone acetyltransferase (HAT) and deacetylase (HDAC) activity in ejaculated sperm and their relevance to conventional sperm parameters. Materials and Methods:Thirty-three normozoospermic men were included in this study. Semen samples were processed by swim-up and then immunostained by six acetylation antibodies (H3K9ac, H3K14ac, H4K5ac, H4K8ac, H4K12ac, and H4K16ac). Our preliminary study verified the expression of HAT/HDAC1 in mature human sperm. From vitrified-warmed sperm samples, total HAT/HDAC activity was measured by commerciallyavailable kits. Nuclear DNA integrity was also measured by TUNEL assay. Results: The levels of six acetylation marks were not related with conventional sperm parameters including sperm DNA fragmentation index (DFI) as well as HAT/HDAC activity. However, sperm DFI was positively correlated with HAT activity (r=0.038 after adjustment, p<0.02). HAT activity showed a negative relationshipwith HDAC activity (r=-0.51, p<0.01). Strict morphology was negatively correlated with acetylation enzyme index (=HAT activity/HDAC activity) (r= -0.53, p<0.01). Conclusion: Our works demonstrated a significant relationship of acetylation-associated enzyme activity and strict morphology or sperm DFI.