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Microtubule acetylation has been shown to regulate actin filament dynamics by modulating signaling pathways that control actin organization, although the precise mechanisms remain unknown. In this study, we found that the downregulation of microtubule acetylation via the disruption ATAT1 (which encodes α-tubulin N-acetyltransferase 1) inhibited the expression of RhoA, a small GTPase involved in regulating the organization of actin filaments and the formation of stress fibers. Analysis of RHOA promoter and chromatin immunoprecipitation assays revealed that C/EBPβ is a major regulator of RHOA expression. Interestingly, the majority of C/EBPβ in ATAT1 knockout(KO) cells was found in the nucleus as a 27-kDa fragment(referred to as C/EBPβp27) lacking the N-terminus of C/EBPβ. Overexpression of a gene encoding a C/EBPβp27-mimicking protein via an N-terminal deletion in C/EBPβ led to competitive binding with wild-type C/EBPβ at the C/EBPβ binding site in the RHOA promoter, resulting in a significant decrease of RHOA expression. We also found that cathepsin L (CTSL), which is overexpressed in ATAT1 KO cells, is responsible for C/EBPβp27 formation in the nucleus. Treatment with a CTSL inhibitor led to the restoration of RHOA expression by downregulation of C/EBPβp27 and the invasive ability of ATAT1 KO MDA-MB-231 breast cancer cells. Collectively, our findings suggest that the downregulation of microtubule acetylation associated with ATAT1 deficiency suppresses RHOA expression by forming C/EBPβp27 in the nucleus through CTSL. We propose that CTSL and C/EBPβp27 may represent a novel therapeutic target for breast cancer treatment.

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기사명 저자명 페이지 원문 목차
Distinctive contribution of two additional residues in protein aggregation of Aβ42 and Aβ40 isoforms Dongjoon Im, Tae Su Choi p. 263-272

Emerging paradigms in cancer cell plasticity Hyunbin D. Huh, Hyun Woo Park p. 273-280

Integrative analysis of microRNA-mediated mitochondrial dysfunction in hippocampal neural progenitor cell death in relation with Alzheimer’s disease A Reum Han, Tae Kwon Moon, Im Kyeung Kang, Dae Bong Yu, Yechan Kim, Cheolhwan Byon, Sujeong Park, Hae Lin Kim, Kyoung Jin Lee, Heuiran Lee, Ha-Na Woo, Seong Who Kim p. 281-286

CDKN2 expression is a potential biomarker for T cell exhaustion in hepatocellular carcinoma Shibo Wei, Yan Zhang, Baeki E. Kang, Wonyoung Park, He Guo, Seungyoon Nam, Jong-Sun Kang, Jee-Heon Jeong, Yunju Jo, Dongryeol Ryu, Yikun Jiang, Ki-Tae Ha p. 287-292

Genetic disruption of ATAT1 causes RhoA downregulation through abnormal truncation of C/EBPβ Jee-Hye Choi, Jangho Jeong, Jaegu Kim, Eunae You, Seula Keum, Seongeun Song, Ye Eun Hwang, Minjoo Ji, Kwon-Sik Park, Sangmyung Rhee p. 293-298

Tumor antigen PRAME is a potential therapeutic target of p53 activation in melanoma cells Yong-Kyu Lee, Hyeon Ho Heo, Nackhyoung Kim, Ui-Hyun Park, Hyesook Youn, Eun-Yi Moon, Eun-Joo Kim, Soo-Jong Um p. 299-304

T-plastin contributes to epithelial-mesenchymal transition in human lung cancer cells through FAK/AKT/Slug axis signaling pathway Soon Yong Park, Hyeongrok Choi, Soo Min Choi, Seungwon Wang, Sangin Shim, Woojin Jun, Jungkwan Lee, Jin Woong Chung p. 305-310

참고문헌 (19건) : 자료제공( 네이버학술정보 )

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번호 참고문헌 국회도서관 소장유무
1 Essays Biochem. 2019 Oct 31;63(5):509-520 미소장
2 Biol Chem. 2006 Sep;387(9):1285-93 미소장
3 Trends Cell Biol. 2020 Sep;30(9):720-735 미소장
4 Biomaterials. 2011 Jun;32(16):3921-30 미소장
5 EMBO J. 1995 Jul 3;14(13):3170-83 미소장
6 Expert Rev Mol Med. 2009 Apr 08;11:e12 미소장
7 Cytoskeleton (Hoboken). 2021 Jun;78(6):232-248 미소장
8 Br J Pharmacol. 2014 Dec;171(24):5507-23 미소장
9 Int J Mol Sci. 2021 Jun 02;22(11): 미소장
10 Biochem Biophys Res Commun. 2017 Sep 23;491(3):754-759 미소장
11 Pharmacol Ther. 2015 Nov;155:105-16 미소장
12 Curr Biol. 2006 Nov 7;16(21):2166-72 미소장
13 EMBO J. 2019 Jun 3;38(11): 미소장
14 Nat Rev Mol Cell Biol. 2014 Dec;15(12):802-12 미소장
15 Biochem Biophys Res Commun. 2017 Jan 1;482(1):8-14 미소장
16 Small GTPases. 2013 Jul-Sep;4(3):141-7 미소장
17 Nat Cell Biol. 2010 May;12(5):457-67 미소장
18 Oncogene. 2003 Feb 13;22(6):869-83 미소장
19 Oncol Rep. 2014 Mar;31(3):1334-42 미소장

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