PLZF is a Negative Regulator of Retinoic Acid Receptor Transcriptional Activity

Overview

Journal Nucl Recept

Date 2003 Oct 3

PMID 14521715

Citations 19

Authors

Perrine J Martin

Marie-Helene Delmotte

Pierre Formstecher

Philippe Lefebvre

Affiliations

Soon will be listed here.

Abstract

BACKGROUND: Retinoic acid receptors (RARs) are ligand-regulated transcription factors controlling cellular proliferation and differentiation. Receptor-interacting proteins such as corepressors and coactivators play a crucial role in specifying the overall transcriptional activity of the receptor in response to ligand treatment. Little is known however on how receptor activity is controlled by intermediary factors which interact with RARs in a ligand-independent manner. RESULTS: We have identified the promyelocytic leukemia zinc finger protein (PLZF), a transcriptional corepressor, to be a RAR-interacting protein using the yeast two-hybrid assay. We confirmed this interaction by GST-pull down assays and show that the PLZF N-terminal zinc finger domain is necessary and sufficient for PLZF to bind RAR. The RAR ligand binding domain displayed the highest affinity for PLZF, but corepressor and coactivator binding interfaces did not contribute to PLZF recruitment. The interaction was ligand-independent and correlated to a decreased transcriptional activity of the RXR-RAR heterodimer upon overexpression of PLZF. A similar transcriptional interference could be observed with the estrogen receptor alpha and the glucocorticoid receptor. We further show that PLZF is likely to act by preventing RXR-RAR heterodimerization, both in-vitro and in intact cells. CONCLUSION: Thus RAR and PLZF interact physically and functionally. Intriguingly, these two transcription factors play a determining role in hematopoiesis and regionalization of the hindbrain and may, upon chromosomal translocation, form fusion proteins. Our observations therefore define a novel mechanism by which RARs activity may be controlled.

Citing Articles

The Contribution of Hippocampal All-Trans Retinoic Acid (ATRA) Deficiency to Alzheimer's Disease: A Narrative Overview of ATRA-Dependent Gene Expression in Post-Mortem Hippocampal Tissue.

Almaguer J, Hindle A, Lawrence J Antioxidants (Basel). 2023; 12(11).

PMID: 38001775 PMC: 10669734. DOI: 10.3390/antiox12111921.

Enhanced ZBTB16 Levels by Progestin-Only Contraceptives Induces Decidualization and Inflammation.

Arlier S, Kayisli U, Semerci N, Ozmen A, Larsen K, Schatz F Int J Mol Sci. 2023; 24(13).

PMID: 37445713 PMC: 10341894. DOI: 10.3390/ijms241310532.

Glucocorticoid signaling induces transcriptional memory and universally reversible chromatin changes.

Bothe M, Buschow R, Meijsing S Life Sci Alliance. 2021; 4(10).

PMID: 34446533 PMC: 8403771. DOI: 10.26508/lsa.202101080.

Comparison of PLZF Gene Expression between Pluripotent Stem Cells and Testicular Germ Cells.

Azizi H, Koruji M, Skutella T Cell J. 2019; 22(1):60-65.

PMID: 31606967 PMC: 6791073. DOI: 10.22074/cellj.2020.6532.

C2H2-Type Zinc Finger Proteins: Evolutionarily Old and New Partners of the Nuclear Hormone Receptors.

Mackeh R, Marr A, Fadda A, Kino T Nucl Recept Signal. 2019; 15:1550762918801071.

PMID: 30718982 PMC: 6348741. DOI: 10.1177/1550762918801071.

References

Collingwood T, Butler A, Tone Y, Clifton-Bligh R, Parker M, Chatterjee V . Thyroid hormone-mediated enhancement of heterodimer formation between thyroid hormone receptor beta and retinoid X receptor. J Biol Chem. 1997; 272(20):13060-5. DOI: 10.1074/jbc.272.20.13060. View

Ball H, Melnick A, Shaknovich R, Kohanski R, Licht J . The promyelocytic leukemia zinc finger (PLZF) protein binds DNA in a high molecular weight complex associated with cdc2 kinase. Nucleic Acids Res. 1999; 27(20):4106-13. PMC: 148680. DOI: 10.1093/nar/27.20.4106. View

Renaud J, Rochel N, Ruff M, Vivat V, Chambon P, Gronemeyer H . Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid. Nature. 1995; 378(6558):681-9. DOI: 10.1038/378681a0. View

Koken M, Daniel M, Gianni M, Zelent A, Licht J, Buzyn A . Retinoic acid, but not arsenic trioxide, degrades the PLZF/RARalpha fusion protein, without inducing terminal differentiation or apoptosis, in a RA-therapy resistant t(11;17)(q23;q21) APL patient. Oncogene. 1999; 18(4):1113-8. DOI: 10.1038/sj.onc.1202414. View

Licht J, Chomienne C, Goy A, Chen A, Scott A, Head D . Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11;17). Blood. 1995; 85(4):1083-94. View

Wang Z, Delva L, Gaboli M, Rivi R, Giorgio M, Cordon-Cardo C . Role of PML in cell growth and the retinoic acid pathway. Science. 1998; 279(5356):1547-51. DOI: 10.1126/science.279.5356.1547. View

Gelmetti V, Zhang J, Fanelli M, Minucci S, Pelicci P, Lazar M . Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO. Mol Cell Biol. 1998; 18(12):7185-91. PMC: 109300. DOI: 10.1128/MCB.18.12.7185. View

Ward J, McConnell M, Carlile G, Pandolfi P, Licht J, Freedman L . The acute promyelocytic leukemia-associated protein, promyelocytic leukemia zinc finger, regulates 1,25-dihydroxyvitamin D(3)-induced monocytic differentiation of U937 cells through a physical interaction with vitamin D(3) receptor. Blood. 2001; 98(12):3290-300. DOI: 10.1182/blood.v98.12.3290. View

Koken M, Reid A, Quignon F, Chelbi-Alix M, Davies J, Kabarowski J . Leukemia-associated retinoic acid receptor alpha fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies. Proc Natl Acad Sci U S A. 1997; 94(19):10255-60. PMC: 23349. DOI: 10.1073/pnas.94.19.10255. View

10.

Li X, Ninan N, Weiner E, Rauscher 3rd F, Marmorstein R . Overexpression, purification, characterization, and crystallization of the BTB/POZ domain from the PLZF oncoprotein. J Biol Chem. 1997; 272(43):27324-9. DOI: 10.1074/jbc.272.43.27324. View

11.

Rachez C, Freedman L . Mediator complexes and transcription. Curr Opin Cell Biol. 2001; 13(3):274-80. DOI: 10.1016/s0955-0674(00)00209-x. View

12.

Zhong S, Salomoni P, Pandolfi P . The transcriptional role of PML and the nuclear body. Nat Cell Biol. 2000; 2(5):E85-90. DOI: 10.1038/35010583. View

13.

Licht J, Shaknovich R, English M, Melnick A, Li J, Reddy J . Reduced and altered DNA-binding and transcriptional properties of the PLZF-retinoic acid receptor-alpha chimera generated in t(11;17)-associated acute promyelocytic leukemia. Oncogene. 1996; 12(2):323-36. View

14.

Zhong S, Delva L, Rachez C, Cenciarelli C, Gandini D, Zhang H . A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins. Nat Genet. 1999; 23(3):287-95. DOI: 10.1038/15463. View

15.

Zhang T, Xiong H, Kan L, Zhang C, Jiao X, Fu G . Genomic sequence, structural organization, molecular evolution, and aberrant rearrangement of promyelocytic leukemia zinc finger gene. Proc Natl Acad Sci U S A. 1999; 96(20):11422-7. PMC: 18049. DOI: 10.1073/pnas.96.20.11422. View

16.

Li J, English M, Ball H, Yeyati P, Waxman S, Licht J . Sequence-specific DNA binding and transcriptional regulation by the promyelocytic leukemia zinc finger protein. J Biol Chem. 1997; 272(36):22447-55. DOI: 10.1074/jbc.272.36.22447. View

17.

Chen S, Zelent A, Tong J, Yu H, Wang Z, Derre J . Rearrangements of the retinoic acid receptor alpha and promyelocytic leukemia zinc finger genes resulting from t(11;17)(q23;q21) in a patient with acute promyelocytic leukemia. J Clin Invest. 1993; 91(5):2260-7. PMC: 288229. DOI: 10.1172/JCI116453. View

18.

Lefebvre P . Molecular basis for designing selective modulators of retinoic acid receptor transcriptional activities. Curr Drug Targets Immune Endocr Metabol Disord. 2002; 1(2):153-64. View

19.

Lefebvre B, Mouchon A, Formstecher P, Lefebvre P . H11-H12 loop retinoic acid receptor mutants exhibit distinct trans-activating and trans-repressing activities in the presence of natural or synthetic retinoids. Biochemistry. 1998; 37(26):9240-9. DOI: 10.1021/bi9804840. View

20.

Sitterlin D, Tiollais P, Transy C . The RAR alpha-PLZF chimera associated with Acute Promyelocytic Leukemia has retained a sequence-specific DNA-binding domain. Oncogene. 1997; 14(9):1067-74. DOI: 10.1038/sj.onc.1200916. View