Characterization of Nuclear Localization and SUMOylation of the ATBF1 Transcription Factor in Epithelial Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Mar 22

PMID 24651376

Citations 16

Authors

Xiaodong Sun

Jie Li

Frederick N Dong

Jin-Tang Dong

Affiliations

Soon will be listed here.

Abstract

ATBF1/ZFHX3 is a large transcription factor that functions in development, tumorigenesis and other biological processes. ATBF1 is normally localized in the nucleus, but is often mislocalized in the cytoplasm in cancer cells. The mechanism underlying the mislocalization of ATBF1 is unknown. In this study, we analyzed the nuclear localization of ATBF1, and found that ectopically expressed ATBF1 formed nuclear body (NB)-like dots in the nucleus, some of which indeed physically associated with promyelocytic leukemia (PML) NBs. We also defined a 3-amino acid motif, KRK2615-2617, as the nuclear localization signal (NLS) for ATBF1. Interestingly, diffusely distributed nuclear SUMO1 proteins were sequestered into ATBF1 dots, which could be related to ATBF1's physical association with PML NBs, known SUMOylation hotspots. Furthermore, ATBF1 itself was SUMOylated. ATBF1 SUMOylation occurred at more than 3 lysine residues including K2349, K2806 and K3258 and was nuclear specific. Finally, the PIAS3 SUMO1 E3 ligase, which interacts with ATBF1 directly, diminished rather than enhanced ATBF1 SUMOylation, preventing the co-localization of ATBF1 with SUMO1 in the nucleus. These findings suggest that nuclear localization and SUMOylation are important for the transcription factor function of ATBF1, and that ATBF1 could cooperate with PML NBs to regulate protein SUMOylation in different biological processes.

Citing Articles

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ATBF1 is a potential diagnostic marker of histological grade and functions via WNT5A in breast cancer.

Li M, Zheng Y, Li X, Shen X, Zhang T, Weng B BMC Cancer. 2022; 22(1):1280.

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Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases.

Lara-Urena N, Jafari V, Garcia-Dominguez M Int J Mol Sci. 2022; 23(14).

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Zfhx3 Transcription Factor Represses the Expression of Gene and Decreases Sodium Current Density (I).

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References

Lallemand-Breitenbach V, de The H . PML nuclear bodies. Cold Spring Harb Perspect Biol. 2010; 2(5):a000661. PMC: 2857171. DOI: 10.1101/cshperspect.a000661. View

Sun X, Li J, Sica G, Fan S, Wang Y, Chen Z . Interruption of nuclear localization of ATBF1 during the histopathologic progression of head and neck squamous cell carcinoma. Head Neck. 2012; 35(7):1007-14. PMC: 3978689. DOI: 10.1002/hed.23077. View

Matsuoka S, Ballif B, Smogorzewska A, McDonald 3rd E, Hurov K, Luo J . ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007; 316(5828):1160-6. DOI: 10.1126/science.1140321. View

Zhang S, Kim T, Dong Y, Kanazawa S, Kawaguchi M, Gao N . AT motif binding factor 1 (ATBF1) is highly phosphorylated in embryonic brain and protected from cleavage by calpain-1. Biochem Biophys Res Commun. 2012; 427(3):537-41. DOI: 10.1016/j.bbrc.2012.09.092. View

Mori Y, Kataoka H, Miura Y, Kawaguchi M, Kubota E, Ogasawara N . Subcellular localization of ATBF1 regulates MUC5AC transcription in gastric cancer. Int J Cancer. 2007; 121(2):241-7. DOI: 10.1002/ijc.22654. View

Burgner D, Davila S, Breunis W, Ng S, Li Y, Bonnard C . A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease. PLoS Genet. 2009; 5(1):e1000319. PMC: 2607021. DOI: 10.1371/journal.pgen.1000319. View

Zimber A, Nguyen Q, Gespach C . Nuclear bodies and compartments: functional roles and cellular signalling in health and disease. Cell Signal. 2004; 16(10):1085-104. DOI: 10.1016/j.cellsig.2004.03.020. View

Mabuchi M, Kataoka H, Miura Y, Kim T, Kawaguchi M, Ebi M . Tumor suppressor, AT motif binding factor 1 (ATBF1), translocates to the nucleus with runt domain transcription factor 3 (RUNX3) in response to TGF-beta signal transduction. Biochem Biophys Res Commun. 2010; 398(2):321-5. DOI: 10.1016/j.bbrc.2010.06.090. View

Shen T, Lin H, Scaglioni P, Yung T, Pandolfi P . The mechanisms of PML-nuclear body formation. Mol Cell. 2006; 24(3):331-9. PMC: 1978182. DOI: 10.1016/j.molcel.2006.09.013. View

10.

Jung C, Uhm K, Miura Y, Hosono T, Horike H, Khanna K . Beta-amyloid increases the expression level of ATBF1 responsible for death in cultured cortical neurons. Mol Neurodegener. 2011; 6:47. PMC: 3145572. DOI: 10.1186/1750-1326-6-47. View

11.

Brand P, Lenser T, Hemmerich P . Assembly dynamics of PML nuclear bodies in living cells. PMC Biophys. 2010; 3(1):3. PMC: 2854101. DOI: 10.1186/1757-5036-3-3. View

12.

Delaune A, Corbiere C, Benjelloun F, Legrand E, Vannier J, Ripoll C . Promyelocytic leukemia-nuclear body formation is an early event leading to retinoic acid-induced differentiation of neuroblastoma cells. J Neurochem. 2007; 104(1):89-99. DOI: 10.1111/j.1471-4159.2007.05019.x. View

13.

Dong X, Fu X, Fan S, Guo P, Su D, Dong J . Oestrogen causes ATBF1 protein degradation through the oestrogen-responsive E3 ubiquitin ligase EFP. Biochem J. 2012; 444(3):581-90. PMC: 3754848. DOI: 10.1042/BJ20111890. View

14.

Nojiri S, Joh T, Miura Y, Sakata N, Nomura T, Nakao H . ATBF1 enhances the suppression of STAT3 signaling by interaction with PIAS3. Biochem Biophys Res Commun. 2004; 314(1):97-103. DOI: 10.1016/j.bbrc.2003.12.054. View

15.

Geiss-Friedlander R, Melchior F . Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol. 2007; 8(12):947-56. DOI: 10.1038/nrm2293. View

16.

Kim T, Kawaguchi M, Suzuki M, Jung C, Asai K, Shibamoto Y . The ZFHX3 (ATBF1) transcription factor induces PDGFRB, which activates ATM in the cytoplasm to protect cerebellar neurons from oxidative stress. Dis Model Mech. 2010; 3(11-12):752-62. DOI: 10.1242/dmm.004689. View

17.

Evdokimov E, Sharma P, Lockett S, Lualdi M, Kuehn M . Loss of SUMO1 in mice affects RanGAP1 localization and formation of PML nuclear bodies, but is not lethal as it can be compensated by SUMO2 or SUMO3. J Cell Sci. 2008; 121(Pt 24):4106-13. DOI: 10.1242/jcs.038570. View

18.

Zhang Z, Yamashita H, Toyama T, Sugiura H, Ando Y, Mita K . ATBF1-a messenger RNA expression is correlated with better prognosis in breast cancer. Clin Cancer Res. 2005; 11(1):193-8. View

19.

Morinaga T, Yasuda H, Hashimoto T, Higashio K, Tamaoki T . A human alpha-fetoprotein enhancer-binding protein, ATBF1, contains four homeodomains and seventeen zinc fingers. Mol Cell Biol. 1991; 11(12):6041-9. PMC: 361769. DOI: 10.1128/mcb.11.12.6041-6049.1991. View

20.

Benjamin E, Rice K, Arking D, Pfeufer A, van Noord C, Smith A . Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat Genet. 2009; 41(8):879-81. PMC: 2761746. DOI: 10.1038/ng.416. View