The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive

André T Hoogeveen1, Stefano Rossetti, Violeta Stoyanova

  • 1Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands. hoogeveen@ikg.fgg.eur.nl

Oncogene
|September 21, 2002
PubMed

Insights

Myeloid Translocation Gene (MTG) proteins are novel corepressors. MTG16a

Area of Science:

  • Molecular Biology
  • Cancer Genetics
  • Epigenetics

Background:

  • Myeloid Translocation Gene (MTG) proteins function as transcriptional corepressors.
  • The MTG16 gene is altered in myeloid malignancies by the t(16;21) translocation.
  • MTG16a is a protein isoform encoded by the MTG16 gene.

Purpose of the Study:

  • To investigate the function and localization of MTG16a.
  • To elucidate the role of MTG16a in the pathogenesis of myeloid malignancies.
  • To characterize the AML1-MTG16 fusion protein resulting from the t(16;21) translocation.

Main Methods:

  • Amino acid sequence mapping to determine nucleolar localization.
  • Interaction studies with histone deacetylases (HDACs).
  • Oligomerization assays for MTG proteins and fusion proteins.

Main Results:

  • MTG16a is localized to the nucleolus via its N-terminal region.
  • MTG16a interacts with HDACs, suggesting a role in gene silencing.
  • The AML1-MTG16 fusion protein localizes to the nucleoplasm and interacts with HDAC1 and HDAC3.

Conclusions:

  • Alterations in MTG16a localization and function due to the t(16;21) translocation may contribute to myeloid malignancies.
  • The interaction of the AML1-MTG16 fusion protein with HDACs and its altered localization are critical in disease pathogenesis.
  • Deficiency of nucleolar HDACs and accumulation at AML1-binding sites are implicated in the development of t(16;21) myeloid malignancies.

Related Concept Videos

The Nucleolus02:55

The Nucleolus

The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Abnormal Proliferation02:23

Abnormal 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...
Master Transcription Regulators02:23

Master 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...
Master Transcription Regulators02:23

Master 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...