Related Experiment Video
Updated: Jul 7, 2026
09:37
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
The human trithorax protein hASH2 functions as an oncoprotein
Juliane Lüscher-Firzlaff1, Isabella Gawlista, Jörg Vervoorts
1Institut für Biochemie, Klinikum, RWTH Aachen University, Aachen, Germany.
Cancer Research
|February 5, 2008
Summary
ASH2 (a protein involved in gene regulation) acts as an oncoprotein, cooperating with MYC and Ha-RAS to drive tumor formation and growth. Increased ASH2 protein levels correlate with human tumors, and its reduction inhibits cancer cell proliferation.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Research
Background:
- Chromatin regulation is crucial for gene expression control.
- Histone modifications, like H3K4me3, are key epigenetic marks.
- ASH2 protein is part of complexes regulating transcription, including those with MLL and MYC oncoproteins.
Purpose of the Study:
- To investigate the role of human ASH2 (hASH2) in cellular transformation.
- To determine if hASH2 functions as an oncoprotein.
- To examine the impact of hASH2 on tumor development and proliferation.
Main Methods:
- Co-immunoprecipitation to identify protein complexes.
- Co-transformation assays using rat embryo fibroblasts (REFs) with oncogenes.
- In vivo tumor formation studies in animal models.
- Analysis of hASH2 mRNA and protein expression in human tumors.
- siRNA-mediated knockdown of hASH2 to assess proliferation.
Main Results:
- hASH2 forms a complex with the oncoprotein MYC.
- hASH2 cooperates with Ha-RAS to transform primary rat embryo fibroblasts.
- Transformation by MYC and Ha-RAS requires rAsh2.
- hASH2/Ha-RAS-transformed cells formed poorly differentiated fibrosarcomas in vivo.
- hASH2 protein, but not mRNA, is elevated in human tumors.
- Knockdown of hASH2 inhibited tumor cell proliferation.
Conclusions:
- hASH2 functions as a novel oncoprotein.
- ASH2 plays a significant role in oncogenesis and tumor progression.
- Targeting hASH2 protein may offer a therapeutic strategy for cancer.
Related Concept Videos
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
00:55DNA Helicases
DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...