Evidence map›Paper›PMID 34174329›Full record

ReviewJournal of molecular biology2022

The Intrinsically Disordered Proteins MLLT3 (AF9) and MLLT1 (ENL) - Multimodal Transcriptional Switches With Roles in Normal Hematopoiesis, MLL Fusion Leukemia, and Kidney Cancer.

Ashish Kabra, John Bushweller

Open access · greenAbstract readReview
In one paragraph

Review in Journal of molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Ashish KabraDept. of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22903, United States.
John BushwellerDept. of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22903, United States; Dept. of Chemistry, University of Virginia, Charlottesville, VA 22904, United States. Electronic address: jhb4v@virginia.edu.
University of Virginia · US

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Thomas P. Loughran · 1987 to 2026
$72.1M
Systems Biology of Bone Marrow Failure and MDS for Precision MedicineRC2DK122533 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI FIGUEROA, MARIA EUGENIA, FLEMING, MARK D · 2019 to 2023
$6.4M
Targeted Small Molecule Inhibitors for Inv(16) LeukemiaR01CA234478 · NCI · UNIVERSITY OF VIRGINIA · PI BUSHWELLER, JOHN HACKETT, CASTILLA, LUCIO H. · 2019 to 2023
$3.4M
AF9(MLLT3) Function in Leukemia and Normal HematopoiesisR01CA233749 · NCI · UNIVERSITY OF VIRGINIA · PI BUSHWELLER, JOHN HACKETT, FIGUEROA, MARIA EUGENIA · 2019 to 2023
$3.2M
Structure/Function of AF9 and MLL-AF9R01CA155328 · NCI · UNIVERSITY OF VIRGINIA · PI BUSHWELLER, JOHN HACKETT, HEMENWAY, CHARLES STANLEY · 2011 to 2015
$2.3M
800 MHZ NMR SPECTROMETER FOR HIGH-END NMR STRUCTURAL STUDIES: AIDSS10RR023035 · NCRR · UNIVERSITY OF VIRGINIA · PI BUSHWELLER, JOHN HACKETT · 2006 to 2006
$2.0M
NCI NIH HHS P30 CA044579NCI NIH HHS R01 CA155328NCI NIH HHS R01 CA233749NCI NIH HHS R01 CA234478NCRR NIH HHS S10 RR023035NIDDK NIH HHS RC2 DK122533
6 · The paper itself

Abstract

AF9 (MLLT3) and ENL (MLLT1) are members of the YEATS family (named after the five proteins first shown to contain this domain: Yaf9, ENL, AF9, Taf14, Sas5) defined by the presence of a YEATS domain. The YEATS domain is an epigenetic reader that binds to acetylated and crotonylated lysines, unlike the bromodomain which can only bind to acetylated lysines. All members of this family have been shown to be components of various complexes with roles in chromatin remodeling, histone modification, histone variant deposition, and transcriptional regulation. MLLT3 is a critical regulator of hematopoiesis with a role in maintaining the hematopoietic stem or progenitor cell (HSPC) population. Approximately 10% of acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) patients harbor a translocation involving MLL (mixed lineage leukemia). In the context of MLL fusion patients with AML and ALL, MLL-AF9 and MLL-ENL fusions are observed in 34 and 31% of the patients, respectively. The intrinsically disordered C-terminal domain of MLLT3 (AHD, ANC1 homology domain) undergoes coupled binding and folding upon interaction with partner proteins AF4, DOT1L, BCOR, and CBX8. Backbone dynamics studies of the complexes suggest a role for dynamics in function. Inhibitors of the interaction of the intrinsically disordered AHD with partner proteins have been described, highlighting the feasibility of targeting intrinsically disordered regions. MLLT1 undergoes phase separation to enhance recruitment of the super elongation complex (SEC) and drive transcription. Mutations in MLLT1 observed in Wilms tumor patients enhance phase separation and transcription to drive an aberrant gene expression program.

Indexed as

Gene FusionHematopoiesisHumansIntrinsically Disordered ProteinsKidney NeoplasmsLeukemia, Biphenotypic, AcuteMutationNeoplasm ProteinsNuclear ProteinsProtein Interaction Domains and MotifsTranscription FactorsWilms TumorIntrinsically Disordered ProteinsMLLT1 protein, humanMLLT3 protein, humanNeoplasm ProteinsNuclear ProteinsTranscription FactorsAF9ENLIDPMLLT1MLLT3

Identifiers

PMID34174329
PMCPMC8695629
OpenAlexW3175736080

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.