These data represent the most extensive compilation of cardiovascular gene expression information to date. They further demonstrate the untapped potential of genome research for investigating questions related to cardiovascular biology and represent a first-generation genome-based resource for molecular cardiovascular medicine.

The RING domain is a conserved zinc finger motif, which serves as a protein-protein interaction interface. Searches of a human heart expressed sequence tag data base for genes encoding the RING domain identified a novel cDNA, named striated muscle RING zinc finger protein (SMRZ). The SMRZ cDNA is 1.9 kilobase pairs in length and encodes a polypeptide of 288 amino acid residues; analysis of the peptide sequence demonstrated an N-terminal RING domain. Fluorescence in situ hybridization localized SMRZ to chromosome 1p33-34. Northern blots demonstrated that SMRZ is expressed exclusively in striated muscle. In the cardiovascular system, SMRZ is more highly expressed in the fetal heart than in the adult heart (slightly higher expression in the ventricle than in the atrium), suggesting that SMRZ is developmentally regulated. SMRZ was found to interact with SMT3b, a ubiquitin-like protein, through the SMRZ-RING domain. This interaction was abolished by mutagenesis of conserved RING domain residues. Transient transfection of SMRZ into C2C12 myoblasts showed localization of SMRZ to the nucleus. These data suggest that SMRZ may play an important role in striated muscle cell embryonic development and perhaps in cell cycle regulation.The zinc finger proteins (ZFPs) 1 are a group of proteins containing zinc finger domains. The finger-like structures are formed by the coordination of conserved cysteines (C) and histidines (H) with zinc ions (1-3). The discovery of the zinc finger domain in the Xenopus transcription factor IIIA (4), together with ongoing cDNA sequencing projects, has led to a significant acceleration in the discovery of ZFP genes. Combinational diversities among the conserved cysteines and histidines of the domain classifies ZFPs into several types: C 2 H 2 , C 2 C 2, C 2 HC, C 2 HC 4 C(HD), C 3 H, and C 3 HC 4 (3, 5-12). These ZFP types have been described in a human heart EST data base survey as well as in an in silico Northern analysis of a total of 15 different tissues (13).The C 3 HC 4 -type zinc finger domain, also termed RING domain, was first described in the sequence of the human ring 1 gene (14). This domain was subsequently found in a number of virus, yeast, plant, and animal proteins, which have various functions such as oncogenesis, signal transduction, peroxisome biogenesis, viral infection, development, transcriptional repression, and ubiquitination (15, 16). The widespread presence of the RING domain in functionally distinct proteins and in many different species indicates that the domain is essential to basic cellular function and is conserved during evolution. With the aid of sequence alignment, the consensus sequence of this domain was defined as CX 2 CX (9 -39) CX (1-3) HX (2-3) CX 2 CX (4 -48) CX 2 C, where X can be any amino acid. Unlike other zinc finger domains, this domain shows a unique cross-brace arrangement on the conserved residues that coordinate the two zinc ions (15,16).Accumulated evidence suggests that the RING domain is mainly involved in protein-protein interactions (15,16...

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Apoptosis (programmed cell death) is an important process which, in conjunction with cell proliferation, maintains cell number homeostasis. Although apoptosis has been more extensively investigated in other tissues [1,2], only recently has this process been suspected as a significant contributor to both disease and normal development of the cardiovascular system [3-6]. Grasping a comprehension of the underlying genetic mechanisms of apoptosis is especially crucial considering that cardiac myocytes irreversibly exit the cell cycle and thus fail to proliferate during pathological conditions. Despite great strides in understanding the molecular pathways of apoptosis, there still remain numerous questions to be answered. Identifying key genes that are involved in the regulatory process of apoptosis in the cardiovascular system will serve as a basis for creating more effective therapeutic treatments in cardiovascular disease and provide an understanding of how cardiac development is modulated. This review provides a brief summary of recent data implicating genes that may be involved in apoptosis in the cardiovascular system. It also outlines the continued usefulness of large-scale generation of expressed sequence tags (ESTs) to establish expression profiles from the cardiovascular system and as a means of identifying potentially significant apoptotic regulators previously characterized in other tissues but not as yet in the cardiovascular system.