Amyloidosis: Insights from Proteomics
ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 12
Authors: Dogan, Ahmet
Abstract
Amyloidoses are a spectrum of disorders caused by abnormal folding and extracellular deposition of proteins. The deposits lead to tissue damage and organ dysfunction, particularly in the heart, kidneys, and nerves. There are at least 30 different proteins that can cause amyloidosis. The clinical management depends entirely on the type of protein deposited, and thus on the underlying pathogenesis, and often requires high-risk therapeutic intervention. Application of mass spectrometry-based proteomic technologies for analysis of amyloid plaques has transformed the way amyloidosis is diagnosed and classified. Proteomic assays have been extensively used for clinical management of patients with amyloidosis, providing unprecedented diagnostic and biological information. They have shed light on the pathogenesis of different amyloid types and have led to identification of numerous new amyloid types, including ALECT2 amyloidosis, which is now recognized as one of the most common causes of systemic amyloidosis in North America.
Molecular cloning, structural characterization, and chromosomal mapping of the human LECT2 gene
GENOMICS
Authors: Yamagoe, S; Kameoka, Y; Hashimoto, K; Mizuno, S; Suzuki, K
Abstract
We originally isolated LECT2 (leukocyte cell-derived chemotaxin 2) as a 16-kDa secreted protein having a human neutrophil chemotactic activity, then cloned human and bovine LECT2 cDNAs and demonstrated the liver-specific expression of the protein. LECT2 is thought to be a multifunctional protein, because it was recently found to be identical to chondromodulin-II, a growth stimulator of chondrocyte cells. We report here the cloning and the structural analysis of the human LECT2 gene, The gene spans approximately 8 kb and consists of four exons and three introns. Primer extension analysis revealed that several transcription initiation sites occur within 70-230 nucleotides upstream of the translation initiation codon, Several transcriptional control sequences relevant to the liver-specific expression have been identified at the 5' untranslated region of the human LECT2 gene. The human LECT2 gene was mapped to chromosome 5q31.1-q32 by fluorescence in situ hybridization. This region contains a cluster of cytokine genes including IL-4, IL-5, and IL-9. (C) 1998 Academic Press.