High impact information on ACTG2

• Hybridization with the 3' untranslated region, which is specific for the human smooth muscle gamma-actin gene, suggests the single gene in the human genome and specific expressions in enteric and aortic tissues [1].
• To elucidate the mechanism(s) of this phenotypic induction, we focused on the molecular regulation of smooth muscle-gamma-actin, whose expression is induced at late stages of smooth muscle differentiation and developmentally restricted to this lineage [2].
• Smooth muscle-gamma-actin promoter-luciferase reporter activity was enhanced by transforming growth factor-beta, and deletion analysis revealed that CArG box 2 in the promoter was necessary for this transcriptional activation [2].
• Expression of mNkx3-1 in heterologous CV-1 fibroblasts was unable to elicit SMGA promoter activity but required the coexpression of serum response factor (SRF) to activate robust SMGA transcription [3].
• These motifs interacted both in the absence of DNA and when both proteins were bound to a SMGA promoter DNA sequence [4].

Biological context of ACTG2

• Previous studies utilizing a heterologous cell transfection strategy from our laboratory identified the smooth muscle gamma-actin (SMGA) gene as a novel molecular target of Nkx 3.1 regulatory activity [5].
• The human gene for smooth muscle actin (enteric type, ACTA3) has been isolated, and three overlapping clones, lambda HACTSG-17, -2, and -112, were used as probes for fluorescence in situ hybridization of human chromosomes [6].
• Moreover, when injected into the cytoplasm, plasmids containing portions of the SMGA promoter localize to the nucleus of smooth muscle cells, but remain cytoplasmic in fibroblasts and CV1 cells [7].
• In gene transfer experiments with SMGA promoter-luciferase reporter gene constructs we observed four- to fivefold stronger SMGA promoter activity in differentiated SMCs relative to replicating visceral smooth muscle cells [8].
• Smooth muscle gamma-actin (SMGA) is both an early marker of smooth muscle cell differentiation, which demonstrates an expression pattern restricted to smooth muscle and the post meiotic spermatocyte [9].

Anatomical context of ACTG2

• A HindIII DNA polymorphism in the human enteric type smooth muscle actin gene (ACTSG) [10].
• In the studies presented here, SMGA gene activity and regulation were evaluated in normal and cancerous prostate epithelial cells [5].
• In the studies reported here, we have further characterized the role of SRF in the regulation of the SMGA gene in the developing gizzard [8].
• This correspondence of SRF and SMGA expression was also observed in cultured smooth muscle mesenchyme induced to express differentiated gene products in vitro [8].
• Keratinocyte spreading was decreased by 78.8% (P = .0006), 80.3% (P = .0001), and 89.2% (P = .0001) on thrombin-, batroxobin-, and ACTE-generated fibrin, respectively, but not on fibrinogen-coated dishes [11].

Associations of ACTG2 with chemical compounds

• The smooth muscle gamma-actin gene is androgen responsive in prostate epithelia [5].
• SMGA transcription was not responsive to steroid in PC-3 prostate epithelial cancer cells, which do not express Nkx 3 [5].
• CP-35,587 was more active than mezlocillin, azlocillin, amoxicillin, ticarcillin and carbenicillin against isolates of K. pneumoniae, but other penicillins were more acte than CP-35,587 against other species of gram-negative bacilli [12].
• Western blot analysis of embryonic chick gizzard whole protein extracts during 5 to 14 days of development demonstrated a large induction of RhoA (10-fold) and beta1 integrin expression at day 8, which corresponds to the time SMGA expression and differentiation are occurring [9].

Regulatory relationships of ACTG2

• 1. However, SMGA transcription was influenced by expression of androgen receptor in these cells, a situation that allows the androgen-dependent expression of Nkx 3 [5].

Analytical, diagnostic and therapeutic context of ACTG2

• We observed an increase in SRF protein and mRNA levels during gizzard development by Western and Northern blot analyses, with a large increase just preceding an increase in SMGA expression [8].

References