Disease relevance of Tagln

• We conclude that loss of transgelin gene expression may be an important early event in tumor progression and a diagnostic marker for breast and colon cancer development [1].
• Mapping of the rat SM22 gene to chromosome 8q24: a candidate for high blood pressure and cardiac hypertrophy [2].

High impact information on Tagln

• 5. The expression of SM22 alpha in smooth muscle cells, as well as early cardiac and skeletal muscle cells, suggests that there may be commonalities between the regulatory programs that direct muscle-specific gene expression in these three myogenic cell types [3].
• To begin to define the mechanisms that regulate the establishment of the smooth muscle lineage, we analyzed the expression pattern of the SM22 alpha gene during mouse embryogenesis [3].
• SM22 alpha is a calponin-related protein that is expressed specifically in adult smooth muscle [3].
• In contrast to its smooth muscle specificity in adult tissues, SM22 alpha was expressed transiently in the heart between E8.0 and E12.5 and in skeletal muscle cells in the myotomal compartment of the somites between E9.5 and E12 [3].
• Loss of transgelin in breast and colon tumors and in RIE-1 cells by Ras deregulation of gene expression through Raf-independent pathways [1].

Biological context of Tagln

• Paralogous sm22alpha (Tagln) genes map to mouse chromosomes 1 and 9: further evidence for a paralogous relationship [4].
• We also found that Ras-dependent and Ras-independent mechanisms can cause the down-regulation of transgelin in human breast and colon carcinoma cells lines and patient-derived tumor samples [1].
• SM22 alpha is a 6.2-kilobase single copy gene composed of five exons [5].
• Transient transfection experiments demonstrated that 441 base pairs of SM22 alpha 5'-flanking sequence was necessary and sufficient to program high level transcription of a luciferase reporter gene in both primary rat aortic SMCs and A7r5 cells [5].
• Both a randomly integrated transgene [SM-CreER(T2)(tg)] and a transgene that has been "knocked in" into the endogenous SM22 locus [SM-CreER(T2)(ki)] were expressed in smooth muscle-containing tissues [6].

Anatomical context of Tagln

• SM22alpha (TAGLN) is one of the earliest markers of differentiated smooth muscle, being expressed exclusively in the smooth muscle cells of adult tissues and transiently in embryonic skeletal and cardiac tissues [4].
• SM22 alpha mRNA is expressed at high levels in the aorta, uterus, lung, and intestine, and in primary cultures of rat aortic SMCs, and the SMC line, A7r5 [5].
• Transgelin was identified previously as a protein whose expression was lost in virally transformed cell lines [1].
• Both cultures expressed stem cell marker CD34 antigen but not protein tyrosine phosphatase, receptor type c. TA and PD cells expressed smooth-muscle cell markers smoothelin and transgelin [7].
• To clarify their relationship we have cloned and sequenced the cDNA encoding Tg from cultures of rat embryo fibroblasts [8].

Associations of Tagln with chemical compounds

• We have generated transgenic mouse lines expressing a tamoxifen-activated Cre recombinase, CreER(T2), under the control of the smooth muscle-specific SM22 promoter [6].
• A functional role for Tg is unlikely to directly involve Ca2+ since it neither contains a functional EF hand nor binds 45Ca2+ [8].
• Cultured VSMC from SM22-PAI+ mice were more resistant to apoptosis induced by tumor necrosis factor plus phorbol myristate acetate or palmitic acid compared with VSMC from negative control littermates [9].
• These markers include Calreticulin, Transgelin, Serotransferrin, Triphosphate isomerase and Carbonic anhydrase II [10].

Regulatory relationships of Tagln

• Co-culture with EC or TGFbeta treatment stimulated activity of a 441-bp SM22-alpha promoter to about the same extent, whereas co-culture induced the activity of a 3.7-kb promoter to about twice that of TGBbeta [11].

Other interactions of Tagln

• We observed that moderate copy number incorporation (four copies) of the A3AR gene driven by the SM22 alpha promoter is sufficient to induce lethality at an early stage of embryo development [12].

Analytical, diagnostic and therapeutic context of Tagln

• In situ hybridization demonstrated that SM22 alpha transcripts were first expressed in vascular smooth muscle cells at about embryonic day (E) 9.5 and thereafter continued to be expressed in all smooth muscle cells into adulthood [3].
• Progressive deletion analysis located the SM22 responsive region of the MMP-9 promoter to the proximal 90-bp region harboring an AP-1 motif subsequently implicated by site-directed mutagenesis [13].
• The reduction of transgelin expression in mouse colon tumors was confirmed by Western blotting and immunohistochemistry [14].
• In S. mansoni infection, low levels of reinfection following chemotherapy are associated with the recognition of a cloned tegumental protein Sm22 [15].
• The proteins recognized by mAb SM22 and SM62 were easily detectable by immunoblotting and immunostaining in Sf9 cells infected with recombinant BV (rBV), but not in non-infected cells [16].

References