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E3 ubiquitin ligase RNF 123 targets lamin B1 and lamin‐binding proteins
Author(s) -
Khanna Richa,
Krishnamoorthy Vidhya,
Parnaik Veena K.
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14477
Subject(s) - lamin , ubiquitin ligase , emerin , microbiology and biotechnology , nuclear lamina , ubiquitin , nuclear protein , cell cycle protein , biology , ddb1 , mutation , chemistry , cell cycle , genetics , cell , nucleus , transcription factor , gene
Lamins are key nuclear proteins which are important for maintaining nuclear structure and function. Mutations in lamins cause a spectrum of genetic diseases termed as laminopathies. RING finger containing E3 ubiquitin ligase, RNF 123, is transcriptionally upregulated in cells expressing rod domain lamin A mutations. However, the functional relevance of RNF 123 in laminopathic cells is not clear. Using a mass spectrometry‐based approach, we identified lamins and lamin‐binding proteins retinoblastoma protein ( pR b), lamina‐associated polypeptide 2α ( LAP 2α), and emerin as RNF 123‐interacting proteins. We determined that RNF 123 mediated the ubiquitination of these proteins and caused the proteasomal degradation of pR b, LAP 2α, and lamin B1. Furthermore, these proteins were also targeted for proteasomal degradation in cells expressing lamin A rod domain mutants G232E, Q294P, and R386K. Overexpression of RNF 123 resulted in delayed transit through the S‐phase which was alleviated by coexpression of pR b or LAP 2α. Our findings imply that RNF 123‐mediated ubiquitination of lamin‐binding proteins may contribute to disease‐causing mechanisms in laminopathies by depletion of key nuclear proteins and defects in cell cycle kinetics.