title: Novel progerin-interactive partner proteins hnRNP E1, EGF, Mel 18, and UBC9 interact with lamin A/C.
abstract: The Hutchinson-Gilford progeria syndrome (HGPS or progeria) is an apparent accelerated aging disorder of childhood. Recently, HGPS has been characterized as one of a growing group of disorders known as laminopathies, which result from genetic defects of the lamin A/C (LMNA) gene. The majority of HGPS mutant alleles involve a silent mutation, c.2063C>T resulting in G608G, that generates a cryptic splicing site in exon 11 of LMNA and consequently truncates 50 amino acids near the C-terminus of pre-lamin A/C. To explore possible mechanisms underlying the development of HGPS, we began a search for proteins that would uniquely interact with progerin (the truncated lamin A in HGPS) using a yeast two-hybrid system. Four new progerin interactive partner proteins were identified that had not been previously found to interact with lamin A/C: hnRNP E1, UBC9 (ubiquitin conjugating enzyme E2I), Mel-18, and EGF1. However, using control and progeria fibroblasts, co-immunoprecipitation studies of endogenous proteins did not show differential binding affinity compared to normal lamin A/C. Thus, we did not find evidence for uniquely interacting partner proteins using this approach, but did identify four new lamin A/C interactive partners.
authors.affiliation: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Nanbert
authors.initials: N
authors.lastname: Zhong
authors.forename: Gabriel
authors.initials: G
authors.lastname: Radu
authors.forename: Weina
authors.initials: W
authors.lastname: Ju
authors.forename: W Ted
authors.initials: WT
authors.lastname: Brown
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011371:Progeria / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D034904:Lamin Type A; C094604:PCBP1 protein, human; C489348:PCGF2 protein, human; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C440308:lamin C; D004815:Epidermal Growth Factor; D044763:Ubiquitin-Conjugating Enzymes; D063150:Polycomb Repressive Complex 1; D000098843:Ubiquitin-Conjugating Enzyme UBC9