6mev › Citations

JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes.

Lee S, Liu H, Hill R, Chen C, Hong X, Crawford F, Kingsley M, Zhang Q, Liu X, Chen Z, Lengeling A, Bernt KM, Marrack P, Kappler J, Zhou Q, Li CY, Xue Y, Hansen K, Zhang G
Elife 9 (2020)
Cited: 17 times
EuropePMC logo PMID: 32048991

Abstract

In animals, an enzyme known as RNA polymerase II (Pol II for short) is a key element of the transcription process, whereby the genetic information contained in DNA is turned into messenger RNA molecules in the cells, which can then be translated to proteins. To perform this task, Pol II needs to be activated by a complex of proteins called P-TEFb; however, P-TEFb is usually found in an inactive form held by another group of proteins. Yet, it is unclear how P-TEFb is released and allowed to activate Pol II. Scientists have speculated that another protein called JMJD6 (Jumonji domain-containing 6) is important for P-TEFb to activate Pol II. Various roles for JMJD6 have been proposed, but its exact purpose remains unclear. Recently, two enzymes closely related to JMJD6 were found to be able to make precise cuts in other proteins; Lee, Liu et al. therefore wanted to test whether this is also true of JMJD6. Experiments using purified JMJD6 showed that it could make a cut in an enzyme called MePCE, which belongs to the group of proteins that hold P-TEFb in its inactive form. Lee, Liu et al. then tested the relationships between these proteins in living human and mouse cells. The levels of activated Pol II were lower in cells without JMJD6 and higher in those without MePCE. Together, the results suggest that JMJD6 cuts MePCE to release P-TEFb, which then activates Pol II. JMJD6 appears to know where to cut by following a specific pattern of elements in the structure of MePCE. When MePCE was mutated so that the pattern changed, JMJD6 was unable to cut it. These results suggest that JMJD6 and related enzymes belong to a new family of proteases, the molecular scissors that can cleave other proteins. The molecules that regulate transcription often are major drug targets, for example in the fight against cancer. Ultimately, understanding the role of JMJD6 might help to identify new avenues for cancer drug development.

Reviews - 6mev mentioned but not cited (2)

  1. Current Status of the Use of Multifunctional Enzymes as Anti-Cancer Drug Targets. Teixeira CSS, Sousa SF. Pharmaceutics 14 10 (2021)
  2. Role of the Epigenetic Modifier JMJD6 in Tumor Development and Regulation of Immune Response. Wang K, Yang C, Li H, Liu X, Zheng M, Xuan Z, Mei Z, Wang H. Front Immunol 13 859893 (2022)

Articles - 6mev mentioned but not cited (3)

  1. JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes. Lee S, Liu H, Hill R, Chen C, Hong X, Crawford F, Kingsley M, Zhang Q, Liu X, Chen Z, Lengeling A, Bernt KM, Marrack P, Kappler J, Zhou Q, Li CY, Xue Y, Hansen K, Zhang G. Elife 9 e53930 (2020)
  2. Smad7 foci are present in micronuclei induced by heavy particle radiation. Wang M, Saha J, Cucinotta FA. Mutat Res 756 108-114 (2013)
  3. Effectiveness and toxicity of cetuximab with concurrent RT in locally advanced cutaneous squamous cell skin cancer: a case series. Chang M, Samlowski W, Meoz R. Oncotarget 14 709-718 (2023)


Reviews citing this publication (5)

  1. The Functions of BET Proteins in Gene Transcription of Biology and Diseases. Cheung KL, Kim C, Zhou MM. Front Mol Biosci 8 728777 (2021)
  2. CDK9 keeps RNA polymerase II on track. Egloff S. Cell Mol Life Sci 78 5543-5567 (2021)
  3. The Pol III transcriptome: Basic features, recurrent patterns, and emerging roles in cancer. Zhou S, Van Bortle K. Wiley Interdiscip Rev RNA 14 e1782 (2023)
  4. Progress in 7SK ribonucleoprotein structural biology. Camara MB, Sobeh AM, Eichhorn CD. Front Mol Biosci 10 1154622 (2023)
  5. The Novel Protease Activities of JMJD5-JMJD6-JMJD7 and Arginine Methylation Activities of Arginine Methyltransferases Are Likely Coupled. Liu H, Wei P, Zhang Q, Chen Z, Liu J, Zhang G. Biomolecules 12 347 (2022)

Articles citing this publication (7)

  1. Epigenome screening highlights that JMJD6 confers an epigenetic vulnerability and mediates sunitinib sensitivity in renal cell carcinoma. Zhang C, Lu X, Huang J, He H, Chen L, Liu Y, Wang H, Xu Y, Xing S, Ruan X, Yang X, Chen L, Xu D. Clin Transl Med 11 e328 (2021)
  2. JMJD6 Regulates Splicing of Its Own Gene Resulting in Alternatively Spliced Isoforms with Different Nuclear Targets. Raguz N, Heim A, Engal E, Wesche J, Merl-Pham J, Hauck SM, Erkelenz S, Schaal H, Bensaude O, Wolf A, Salton M, Böttger A. Int J Mol Sci 21 E6618 (2020)
  3. A specific JMJD6 inhibitor potently suppresses multiple types of cancers both in vitro and in vivo. Xiao RQ, Ran T, Huang QX, Hu GS, Fan DM, Yi J, Liu W. Proc Natl Acad Sci U S A 119 e2200753119 (2022)
  4. Effectors and effects of arginine methylation. Wang Y, Bedford MT. Biochem Soc Trans 51 725-734 (2023)
  5. Catalytic activity of the Bin3/MePCE methyltransferase domain is dispensable for 7SK snRNP function in Drosophila melanogaster. Palumbo RJ, Yang Y, Feigon J, Hanes SD. Genetics 226 iyad203 (2024)
  6. JMJD5 couples with CDK9 to release the paused RNA polymerase II. Liu H, Ramachandran S, Fong N, Phang T, Lee S, Parsa P, Liu X, Harmacek L, Danhorn T, Song T, Oh S, Zhang Q, Chen Z, Zhang Q, Tu TH, Happoldt C, O'Conner B, Janknecht R, Li CY, Marrack P, Kappler J, Leach S, Zhang G. Proc Natl Acad Sci U S A 117 19888-19895 (2020)
  7. JMJD8 Functions as a Novel AKT1 Lysine Demethylase. Wang Y, Zhang Y, Li Z, Wang J. Int J Mol Sci 24 460 (2022)


Quick links