Metastatic Lymph Node 51, a novel nucleo-cytoplasmic protein overexpressed in breast cancer

Abstract

Metastatic Lymph Node 51 (MLN51) cDNA was isolated by differential screening of a human breast cancer metastasis cDNA library. MLN51 cDNA encodes a novel human protein of 703 residues that shares no significant homology to any known protein. However MLN51 is well conserved between vertebrate and invertebrate species suggesting an important biological function. The amino terminal half of the protein contains a coiled-coil domain and two potential nuclear localization signals (NLS). The carboxy terminal half contains one SH2 and four SH3 binding motifs. The coiled-coil domain promotes MLN51 oligomerization in transfected cells. When transiently expressed, the MLN51 protein is mainly found in the cytoplasm with a weak nuclear staining. However, deletion of the carboxy terminal half of the protein allows the targeting of the protein to the nucleus, demonstrating that the NLSs are functional. MLN51 is ubiquitously expressed in normal tissues. Human breast carcinomas show MLN51 overexpression in malignant epithelial cells. The uncommon association of protein -protein interaction domains often found either in nuclear or in cytoplasmic signaling proteins raises a possible nucleo-cytoplasmic function for MLN51.

EJC core component MLN51 interacts with eIF3 and activates translation

“…Therefore, additional experiments will be necessary to determine whether the variation in EJCs and notably the variability in MLN51 and eIF3 provide a way to fine-tune protein synthesis. Finally, MLN51 originally was isolated because of its overexpression in several types of breast cancers (7,38,39). It is tempting to speculate that the differences in MLN51 expression levels may enhance the expression of multiple mRNAs and hence may contribute to cancer progression.…”

Genomic analysis of the HER2/TOP2A amplicon in breast cancer and breast cancer cell lines

“…CASC3 or MLN51 is overexpressed in breast cancers and encodes a core component of the exon junction protein complex, which is deposited on spliced mRNAs at exon-exon junctions and functions in nonsensemediated mRNA decay. 33 RARA is frequently rearranged in promyelocytic leukaemias and has recently been reported to be a separate amplicon in breast cancers with complex patterns of 17q rearrangements. 34 Our findings demonstrate that RARA does not form a separate amplicon and is actually part of TOP2A amplicon.…”

Association of the Breast Cancer Protein MLN51 with the Exon Junction Complex via Its Speckle Localizer and RNA Binding Module

“…All vectors were verified by sequencing from both strands. The pCR3.1-MLN51, pEGFP-Rev-NES, and pSG5-Lasp-1 expression vectors have been described before (4,33,34).…”

“…MLN51 is a nucleocytoplasmic protein containing, within its amino-terminal half, a coiled-coil domain followed by two nuclear localization signals responsible for its nuclear localization. Its carboxyl-terminal half contains putative Src homology domains 2 and 3 binding sites and mediates its cytoplasmic retention (4). Finally, MLN51 is well conserved during evolution in mammals as well as in more distant species such as worm and fly.…”

“…MLN51 presents a correlated pattern of gene amplification and transcript overexpression in breast cancers and cancer-derived cell lines (1)(2)(3). In addition, elevated quantities of MLN51 protein have been found in 30% of primary breast tumor samples tested, although no correlation between MLN51 overexpression and a specific histological tumor type or grade has been found (4). MLN51 is a nucleocytoplasmic protein containing, within its amino-terminal half, a coiled-coil domain followed by two nuclear localization signals responsible for its nuclear localization.…”