Expression of novel ING variants is regulated by thyroid hormone in the Xenopus laevis tadpole

Autor: Rachel C. Skirrow, Randal N. Johnston, Caren C. Helbing, Markéta Gogela-Spehar, Mary J. Wagner, Karl Riabowol
Rok vydání: 2001
Předmět:
Male
Cellular differentiation
Xenopus
Receptors
Cytoplasmic and Nuclear
Apoptosis
Xenopus Proteins
Biochemistry
Culture Media
Serum-Free
Mice
Xenopus laevis
Transcription (biology)
Protein Isoforms
Genes
Tumor Suppressor
Tissue Distribution
Cloning
Molecular
Receptors
Thyroid Hormone
Reverse Transcriptase Polymerase Chain Reaction
Metamorphosis
Biological
Cell Differentiation
Triiodothyronine
Female
Signal transduction
Cell Division
Signal Transduction
Gene isoform
Thyroid Hormones
DNA
Complementary
Blotting
Western
Molecular Sequence Data
Cell fate determination
Biology
Organ Culture Techniques
Animals
Humans
Cell Lineage
Amino Acid Sequence
RNA
Messenger
Molecular Biology
Gene Library
Cell Nucleus
Homeodomain Proteins
Base Sequence
Sequence Homology
Amino Acid
Tumor Suppressor Proteins
Alternative splicing
Cell Biology
biology.organism_classification
Blotting
Northern
Molecular biology
Protein Structure
Tertiary
Alternative Splicing
Homeobox
Zdroj: The Journal of biological chemistry. 276(50)
ISSN: 0021-9258
Popis: The candidate tumor suppressor gene, ING1, encodes several protein isoforms as a result of alternative splicing that may possess agonistic and antagonistic roles in the control of cell proliferation and apoptosis. Recently a related gene, ING2, was isolated in human whose expression is increased in adenocarcinomas. Little is known about the cellular function and regulation of these ING family members, but the fact that ING proteins contain a plant homeodomain finger suggests that these proteins may modulate transcription factor-mediated pathways. To elucidate how ING may interact in different tissues to modulate function, we used amphibian metamorphosis as a model system in which a single stimulus, thyroid hormone (TH), initiates tissue-specific proliferation, differentiation, and apoptosis. We have isolated the first Xenopus laevis ING2 and demonstrate that transcript levels increase in response to TH treatment. We provide evidence for the existence of splice variants that are differentially expressed in tissues with different TH-induced fates. Western blots using an antibody directed against the highly conserved C-terminal end of ING proteins reveal a tissue-specific pattern of ING isoform expression in adult Xenopus tissues. Analyses of premetamorphic tadpole tissues show a TH-induced accumulation of ING proteins in tail, whereas the levels in the leg are not affected. This TH-induced accumulation is also observed in serum-free tail organ cultures and is prevented by inhibitors of tail apoptosis. Therefore, this work presents the first link between ING expression and a hormonally regulated nuclear transcription factor-mediated apoptotic response opening the possibility that ING family members may be involved in transducing the signal initiated by TH that determines cell fate.
Databáze: OpenAIRE
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