SMAD5, a transducer of TGF-beta/BMP inhibitory signals and a tumor suppressor candidate, localizes to the region of invariant loss in human myeloid neoplasms, on chromosome 5q31.1. Recent evidence indicates a gene-dosage effect along the TGF-beta/BMP signaling pathways. We have identified a novel transcript designated DAMS, whose 3' exonic sequences contain in part an alternate 5' exon of SMAD5, in the antisense orientation. Expressed sequenced tags (ESTs) for DAMS are found in fetal tissues (heart, adrenal glands, and total fetus) and pancreatic tumor cDNA libraries. In contrast to SMAD5, DAMS expression is not readily detectable in adult and fetal tissues. Semiquantitative PCR suggests that the stoichiometry between SMAD5 and DAMS transcripts ranges between 15 and 120 in normal and malignant hematopoietic cells. The findings raise the possibility that DAMS may be a fail-safe mechanism for precise regulation of SMAD5 transcript levels that may be critical in maintaining normal homeostasis.
- MeSH
- 5' Untranslated Regions genetics MeSH
- RNA, Antisense genetics MeSH
- DNA-Binding Proteins genetics MeSH
- Phosphoproteins genetics MeSH
- Transcription, Genetic genetics MeSH
- Hematopoiesis genetics MeSH
- Humans MeSH
- Chromosomes, Human, Pair 5 genetics MeSH
- RNA, Messenger metabolism MeSH
- Molecular Sequence Data MeSH
- Leukemia, Myeloid genetics MeSH
- Tumor Cells, Cultured MeSH
- Polymerase Chain Reaction MeSH
- Smad5 Protein MeSH
- Gene Expression Regulation, Neoplastic genetics MeSH
- RNA, Long Noncoding MeSH
- RNA, Neoplasm genetics MeSH
- Trans-Activators genetics MeSH
- Transcription Factors genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Names of Substances
- 5' Untranslated Regions MeSH
- RNA, Antisense MeSH
- DNA-Binding Proteins MeSH
- Phosphoproteins MeSH
- RNA, Messenger MeSH
- Smad5 Protein MeSH
- RNA, Long Noncoding MeSH
- RNA, Neoplasm MeSH
- SMAD5 protein, human MeSH Browser
- SMAD5-AS1 lncRNA, human MeSH Browser
- Trans-Activators MeSH
- Transcription Factors MeSH