Anti-cofilin (Phospho-Ser3) Antikörper (A50175)

Phactr proteins bind actin and protein phosphatase 1 (PP1), and are involved in processes ranging from angiogenesis to cell cycle regulation. Phactrs share a highly conserved RPEL domain with the myocardin-related transcription factor (MRTF) family, where actin binding to this domain regulates both the nuclear localization and the activity of these transcription coactivators. We show here that in contrast to MRTF-A, the RPEL domain is dispensable for the subcellular localization of Phactr4. Instead, we find the domain facilitating competitive binding of monomeric actin and PP1 to Phactr4. Binding of actin to Phactr4 influences the activity of PP1 and the phosphorylation status of one of its downstream targets, cofilin. Consequently, at low actin monomer levels, Phactr4 guides PP1 to dephosphorylate cofilin. This active form of cofilin is then able to sever and depolymerize actin filaments and thus restore the actin monomer pool. Accordingly, our data discloses the central role of Phactr4 in a feedback loop, where actin monomers regulate their own number via the activation of a key regulator of actin dynamics. Depending on the protein context, the RPEL domain can thus elicit mechanistically different responses to maintain the cellular actin balance.

p57 is a multifunctional protein involved in the regulation of tumor formation and development; however, the biological role of p57 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. To explore the role of p57 in the development of HCC, we examined p57 messenger RNA (mRNA) and protein levels in HCC tissues and adjacent non-cancerous tissues by immunohistochemistry, real-time polymerase chain reaction and western blot analysis. Moreover, we generated stable p57 knockdown HCC cell lines to investigate the impact of p57 downregulation on the growth and invasion of HCC in vitro and in vivo. Our results showed that p57 mRNA and protein levels were significantly decreased in human HCC tissues. In addition, this reduction in p57 expression was associated with increased tumor size, more advanced TNM stages, the presence of capsule invasion and extrahepatic metastasis and decreased overall survival time. In human HCC cell lines, p57 downregulation increased the expression of cyclin D1 and CDK2 and enhanced the activities of CDK4/cyclin D1 and CDK2/cyclin E complexes, resulting in increased cellular proliferation and growth of xenografts. Furthermore, p57 downregulation accelerated the invasion of HCC cells in vitro and in vivo by controlling the activity of LIMK1. In conclusion, the downregulation of p57 accelerates the growth and invasion of HCC, indicating that p57 is an important tumor suppressor in HCC. Based on these findings, p57 may be a potential target for HCC prevention and therapy.