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mrtl—A translation/localization regulatory protein encoded within the human c‐ myc locus and distributed throughout the endoplasmic and nucleoplasmic reticular network
Author(s) -
Choi Hyoungsoo,
Jackson Nateka L.,
Shaw Denise R.,
Emanuel Peter D.,
Liu Y. Lucy,
Tousson Albert,
Meng Zheng,
Blume Scott W.
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21909
Subject(s) - biology , endoplasmic reticulum , microbiology and biotechnology , ectopic expression , rna binding protein , rna , gene , genetics
Abstract mrtl ( myc ‐ r elated t ranslation/ l ocalization regulatory factor) is a previously uncharacterized protein synthesized from the first open reading frame contained within the human c‐ myc P0 transcript, ∼800 nucleotides upstream of the Myc coding sequence. The mrtl protein, 114 amino acids in length, is projected to contain an N‐terminal transmembrane domain and a highly charged C‐terminal interaction domain with homology to numerous RNA‐binding proteins. Using monoclonal antibodies raised against the hydrophilic C‐terminal domain, endogenous mrtl was visualized in human breast tumor cell lines and primary mammary epithelial cells at the nuclear envelope and contiguous endoplasmic/nucleoplasmic reticulum. mrtl colocalizes and coimmunoprecipitates with translation initiation factor eIF2α and the 40S ribosomal protein RACK1, and appears capable of binding specifically to the c‐ myc RNA. Inducible ectopic overexpression of wild‐type mrtl interferes with the function of endogenous mrtl, which results in loss of Myc from the nucleus. Furthermore, treatment of cells with a peptide derived from the C‐terminal domain displaces endogenous mrtl and causes a dramatic reduction in total cellular Myc protein levels. Together with our previous work demonstrating complete loss of tumorigenicity in association with ectopic expression of the c‐ myc P0 5′‐UTR (containing the mrtl coding sequence), these results suggest that mrtl may serve an important function in regulating Myc translation and localization to the nucleus, perhaps ultimately contributing to the role of the c‐ myc locus in oncogenesis. J. Cell. Biochem. 105: 1092–1108, 2008. © 2008 Wiley‐Liss, Inc.