LIM domains-containing protein 1 (LIMD1) is encoded at chromosome 3p21.3, a region commonly deleted in many solid malignancies. However, the function of LIMD1 is unknown. Here we show that LIMD1 specifically interacts with retinoblastoma protein (pRB), inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. LIMD1 blocks tumor growth in vitro and in vivo and is down-regulated in the majority of human lung cancer samples tested. Our data indicate that LIMD1 is a tumor-suppressor gene, the protein product of which functionally interacts with pRB and the loss of which promotes lung carcinogenesis.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC534532 | PMC |
http://dx.doi.org/10.1073/pnas.0407123101 | DOI Listing |
Cell Death Dis
November 2021
Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M6 BQ, UK.
An early event in lung oncogenesis is loss of the tumour suppressor gene LIMD1 (LIM domains containing 1); this encodes a scaffold protein, which suppresses tumorigenesis via a number of different mechanisms. Approximately 45% of non-small cell lung cancers (NSCLC) are deficient in LIMD1, yet this subtype of NSCLC has been overlooked in preclinical and clinical investigations. Defining therapeutic targets in these LIMD1 loss-of-function patients is difficult due to a lack of 'druggable' targets, thus alternative approaches are required.
View Article and Find Full Text PDFBiochim Biophys Acta Rev Cancer
December 2021
UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:
PDZ and LIM domains-containing proteins play pivotal functions in cell cytoskeleton organization, cell polarization and differentiation. As a key member of the family, PDLIM2 regulates stability and activity of transcription factors such as NF-κB, STATs and β-catenin, and thus exert it functions in inflammation, immunity, and cancer. PDLIM2 functions as a tumor suppressor in multiple tissues and it is often genetically mutated or epigenetically silenced in human cancers derived from lung, breast, ovarian and other histologies.
View Article and Find Full Text PDFJ Fish Biol
November 2021
Institute of Fisheries Science, Tibet Academy of Agricultural and Animal Husbandry Sciences, Lhasa, China.
Background: This study aimed to reveal the biological function and molecular mechanism of phosphorylated proteins in the normal liver (NG) and Exo-celiac liver (WG) of Glyptosternum maculatum and potential plateau-adaption mechanisms of G. maculatum.
Methods: A multivariate analysis was performed on proteomic quantitative data (label-free group) and phosphorylated proteome data (phosphorylation group) to reveal protein characteristics.
Genetics intersects with environmental, cultural, and social factors in the development of addictive disorders. This study reports the feasibility of whole-exome sequencing of trios (subject and two family members) to discover potential genetic variants in the development of substance use disorders (SUD). Family trios were recruited from the National Addictions Management Service in Singapore during the 2016-2018 period.
View Article and Find Full Text PDFChem Sci
September 2020
Institute of Biomedical Sciences, Academia Sinica Taipei 115 Taiwan
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!