Expression of leukemic MLL fusion proteins in Drosophila affects cell cycle control and chromosome morphology

Oncogene
Inhua Muyrers-ChenRenato Paro

Abstract

The Mixed Lineage Leukemia (MLL) gene is involved in lymphoblastic and myeloid leukemia through chromosome translocations leading to fusion of MLL to partner genes, or through internal MLL rearrangements. MLL is the mammalian counterpart of the Drosophila trithorax (trx) gene, involved in maintaining active gene expression states. We have used transgenic Drosophila to assess the molecular targets and cellular processes affected by MLL and two of its leukemic fusion proteins. We find that whereas expression of normal human MLL in flies does not result in phenotypic alterations, overexpressing the human MLL-AF9 and MLL-AF4 proteins causes larval to pupal lethality, which interestingly resembles the phenotypes displayed by certain Drosophila trx mutant alleles. MLL-AF9 and MLL-AF4 transgenic flies exhibit antagonistic alterations in cell cycle progression. Additionally, flies expressing MLL-AF9 display impairment in higher order chromatin integrity, evidenced in decondensation of mitotic figures. The effects of MLL fusion proteins in Drosophila suggest that alteration of chromatin structure by MLL fusion proteins may contribute to the lethal phenotype. Our results indicate that the mode(s) of action of MLL-AF9 in Drosophila varies...Continue Reading

References

Jan 1, 1995·Advances in Cancer Research·E CanaaniC M Croce
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·N J Zeleznik-LeJ D Rowley
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·Q MaA M Buchberg
Dec 19, 1995·Proceedings of the National Academy of Sciences of the United States of America·R PrasadE Canaani
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·T YanoE Canaani
Nov 14, 1997·Developmental Biology·R BernardoniA Giangrande
Oct 17, 1998·Molecular and Cellular Biology·B Hendrich, A Bird
Apr 7, 1999·Nature Genetics·E HeardP Avner
Jun 23, 1999·Current Opinion in Genetics & Development·M van Lohuizen
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·R D HansonS J Korsmeyer
Jul 5, 2001·Molecular and Cellular Biology·S A KrauseM M Heck
Sep 12, 2002·Trends in Molecular Medicine·Emma C Collins, Terence H Rabbitts
Sep 27, 2002·Genesis : the Journal of Genetics and Development·Deborah A KimbrellKathy Beckingham
Nov 28, 2002·Molecular Cell·Thomas A MilneJay L Hess
Feb 15, 2003·Genetics·H AshaCharles R Dearolf
Sep 4, 2003·Genes & Development·Paul M Ayton, Michael L Cleary

❮ Previous
Next ❯

Citations

Apr 5, 2007·Nature Protocols·Roderick A F MacLeodHans G Drexler
Nov 24, 2011·Nature Reviews. Molecular Cell Biology·Bernd SchuettengruberGiacomo Cavalli
Jun 17, 2005·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Michèle J Hoffmann, Wolfgang A Schulz
Aug 18, 2005·International Journal of Hematology·Mariko EguchiMel Greaves
May 13, 2014·Experimental Hematology·Koen H M PrangeJoost H A Martens
Dec 1, 2004·Annual Review of Genetics·Leonie Ringrose, Renato Paro
Aug 16, 2008·Proteins·Kazimierz O Wrzeszczynski, Burkhard Rost
Jul 28, 2020·Cells·Amani Al OutaMargret Shirinian
Sep 23, 2020·Nature Reviews. Genetics·Bercin K Cenik, Ali Shilatifard

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.