Zavadil J, Svoboda P, Liang H, Kottickal L V, Nagarajan L
Department of Cell Physiology, Institute of Hematology and Blood Transfusion, Prague, 12820, Czech Republic.
Biochem Biophys Res Commun. 1999 Feb 24;255(3):668-72. doi: 10.1006/bbrc.1999.0256.
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.
SMAD5是转化生长因子-β/骨形态发生蛋白（TGF-β/BMP）抑制信号的转导分子及肿瘤抑制候选基因，定位于人髓系肿瘤中5号染色体5q31.1上的恒定缺失区域。近期证据表明，TGF-β/BMP信号通路存在基因剂量效应。我们鉴定出一种名为DAMS的新转录本，其3'外显子序列部分包含SMAD5的一个反向5'外显子。在胎儿组织（心脏、肾上腺和全胎）及胰腺肿瘤cDNA文库中发现了DAMS的表达序列标签（EST）。与SMAD5不同，在成人及胎儿组织中不易检测到DAMS的表达。半定量PCR表明，在正常和恶性造血细胞中，SMAD5与DAMS转录本之间的化学计量比在15至120之间。这些发现提示，DAMS可能是精确调控SMAD5转录本水平的一种故障安全机制，这对维持正常内环境稳定可能至关重要。
