Lasp-1, a Novel Type of Actin-Binding Protein Accumulating in Cell Membrane Extensions

Abstract

The Lasp-1 gene, which has been localized to the q12-q2 1 region of human chromosome 17, is amplified and overexpressed in human breast cancers. In addition to the previously reported LIM and SH3 domains of Lasp-1, we report here the identification of an actin-binding domain in the core of the protein. This domain is functional as we demonstrate that Lasp-1 binds actin in vivo and in vitro. In addition, confocal analysis of the Lasp-1 subcellular distribution shows that the protein is colocal

Identification of Src transformation fingerprint in human colon cancer

“…Using our 'transformation fingerprint', we identified several dysregulated genes involved in maintaining cell structure, shape and motility that were up-regulated in both the highly transformed cell lines and human colon tumors. Lasp-1, a novel actin-binding protein that is amplified in breast tumors (Schreiber et al, 1998), is postulated to play an important role in the regulation of dynamic actin-based, cytoskeletal activities (Chew et al, 2000). APP-1 was recently suggested to play a role in actin based cell motility (Sabo et al, 2001) and has been implicated in cell adhesion and proliferation .…”

Nuclear localisation of LASP-1 correlates with poor long-term survival in female breast cancer

“…It became the first member of a newly defined LIM-protein subfamily of the nebulin group characterised by the combined presence of LIM and SH3 domains (Grunewald and Butt, 2008). LASP-1 is localised within multiple sites of dynamic F-actin assembly such as focal contacts, lamellipodia and membrane ruffles it binds to the specific shuttle proteins Zyxin and lipoma preferred partner (LPP) and is involved in cell migration and proliferation (Schreiber et al, 1998;Chew et al, 2002;Butt et al, 2003;Nakagawa et al, 2006). Silencing of LASP-1 by RNA-interference in various cancer cell lines resulted in strong inhibition of proliferation and migration with cell cycle arrest in G2/M-phase (Grunewald et al, 2006(Grunewald et al, , 2007b.…”

The human LASP1 gene is fused to MLL in an acute myeloid leukemia with t(11;17)(q23;q21)

“…(b) Putative MLL/LASP1 and LASP1/MLL fusion proteins. The protein domains of MLL and LASP1 have been extensively analyzed (reviewed in Tomasetto et al, 1995a;Schreiber et al, 1998b;Ayton and Cleary, 2001;Ernst et al, 2002). (c) Direct sequencing of the RT-PCR products performed by MWG-Biotech (Germany) revealed that the MLL/LASP1 and the LASP1/MLL fusion transcripts were both in frame fusions Human LASP1 (LIM and SH3 protein 1) was initially cloned from a breast-cancer-derived metastatic lymph node and is amplified and overexpressed in 12% of breast cancers (Tomasetto et al, 1995a, b).…”

“…LASP1 encodes a putative protein of 261 residues and in addition to an LIM domain at the N-terminus, it also contains an SH3 (Src homology 3) domain at the Cterminus and two actin-binding repeats ( Figure 2b). As a result of this currently unique combination of proteinprotein-interacting domains, LASP1 has recently been categorized as the first member of a new LIM domain containing protein subfamily (Tomasetto et al, 1995a;Schreiber et al, 1998b). LIM and SH3 domains are known to mediate protein-protein interactions involved in the regulation of protein activity.…”