Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells

Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis

“…One could speculate that enhanced levels of Jun : Fra2 dimers will a ect cell motility and invasiveness , in line with the role of Jun : Fos in remodeling of the extra-cellular matrix and the presumed role of Jun : Fos during the later stages of oncogenesis (including metastasis) in rodents (Angel and Karin, 1991;Hofmann et al, 1993;Saez et al, 1995;Hennigan et al, 1994;Lamb et al, 1997;Spence et al, 2000).…”

Transcription factors control invasion: AP-1 the first among equals

“…Like ezrin, Krp1 is located at the tips of extending pseudopods, where it colocalizes with F-actin in membrane ruffles. Increased expression of Krp1 enhances the length of pseudopod extensions in both Fos and Ras transformed fibroblasts Spence et al, 2000). Downregulation of Krp1 expression by siRNA results in truncated pseudopods (Figure 2) (Spence et al, , 2006 and inhibits invasion of (Unpublished data).…”

Regulation of a multigenic invasion programme by the transcription factor, AP-1: re-expression of a down-regulated gene, TSC-36, inhibits invasion

“…84% of the cDNAs subjected to Northern analysis were upregulated in both FBRs and RASs indicating the majority of the cDNAs were not unique to Fos transformation. 57% of the cDNAs were up-regulated after a 24-h treatment with 100 ng/ml of EGF, which is su cient to morphologically transform approximately 50% of the cells (Kaplan and Ozanne, 1982;Lamb et al, 1997a;Spence et al, 2000), and to induce invasion over three days (Hennigan et al, 1994;Lamb et al, 1997a). Expression of 86% of the URL cDNAs is reduced in the FBR-TA cells, indicating an involvement of AP-1, either directly or indirectly, in their expression.…”

“…Herein, we use PCR suppression subtraction hybridization to test whether genes which are up-or down-regulated as a consequence of FBR-vfos transformation constitute a multigenic invasion programme. Previously, we have demonstrated that genes which are up-regulated in Fos-transformed cells are necessary for invasion (Lamb et al, 1997a,b;Spence et al, 2000). We have tested whether genes from the down-regulated library might function as invasion suppressors, by expressing one of the down regulated genes, TSC-36/Frp, in FBRs and assessing the invasiveness of the expressing cells.…”