The LATS tumor suppressor, conserved from Drosophila (dlats) to humans (LATS1, LATS2), plays a vital role in maintaining cellular homeostasis in humans since loss of either LATS1 or LATS2 leads to the development of numerous cancer types such as breast cancer and leukemia 1. Apart from its roles as a Ser/Thr kinase within the emerging Hippo pathway regulating cell proliferation and apoptosis, ultimately leading to the control of organ size and tumorigenesis 2, LATS is also implicated in a broad range of functions including regulation of genetic stability, transcription, and protein stability 1. Recently, tumor suppressors have also been shown to affect the later stages of tumorigenesis, including metastasis. Among this group of metastasis regulators are genes that can directly affect actin dynamics by binding to F-actin, such as the tumor suppressors p53 3, NF2 4 and APC 5. In this study we show that the LATS1 tumor suppressor is also a novel actin-binding protein that can modulate actin polymerization, cell migration, and cell spreading.

Combined with mass spectrometry, SILAC (Stable Isotope Labelled by Amino acids in Cell culture) is a powerful tool for the identification of specific protein-protein interactions. Applying this approach to identifying novel LATS1 interaction partners, LATS1-KO MEFs (LATS1 knockout mouse embryonic fibroblasts) and LATS1-WT-myc MEFs (LATS1 knockout MEFs infected with wild-type myc-tagged LATS1 lentivirus) were labeled with “light” (L) or “heavy” (H) amino acids, respectively, and cell lysate was extracted, immunoprecipitated for LATS1 and mixed elutes subjected to mass spectrometry analysis. From this screen, several novel LATS1-interacting partners were identified (unpublished results). Importantly, we identified β-action as a binding partner of LATS1 (Supplementary information Figure S1). Compared to 40S ribosomal protein S3, a housekeeping gene, with a relative abundance ratio of 1.02, β-actin has a H/L ratio of 1.91, suggesting that β-actin is a novel LATS1 binding partner.

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