Transcription regulation: The Mediator complex is a set of protein coactivators that bridges DNA-binding transcription factors to transcriptional activation of the RNA polymerase II (pol II). MED28 was identified as a subunit of the mammalian Mediator complex by the multidimensional protein identification technology (MudPIT) (Sato et al., 2004). This identification indicates a role of MED28 in the regulation of gene transcription.
Cytoskeletal organization: The implication of MED28 in cytoskeletal re-organization was based on the observation that MED28, similar to merlin, co-localizes with the actin cytoskeleton as determined by cofractionation, immunofluorescence and electron microscopy (Wiederhold et al., 2004).
Signal transduction: Ectopic expression of MED28 led to increased phosphorylation of mitogen-activated protein kinases (MAPK) (Lu et al., 2005). In contrast, MED28-specific knockdown resulted in decreased expression of mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1) in MCF7 cells (Huang et al., 2012). In addition, overexpression of MED28 resulted in the activation of c-Src (Lu et al., 2006) and MED28 can be phosphorylated at Y64 by Fyn, a Src family member (Lee et al., 2006). These data indicate that MED28 may function as a regulator of cellular signal transduction pathways.
Cell proliferation: Ectopic overexpression of MED28 resulted in enhanced cell growth in immortal human embryonic kidney (HEK) 293 cells, and breast cancer cell lines, MCF7 and MDA-MB-231 (Lu et al., 2005). The HEK293 xenograft tumor growth was also stimulated in MED28-overexpressing cells (Lu et al., 2005).
Smooth muscle cell differentiation: MED28 functions a repressor of smooth muscle cell (SMC) differentiation (Beyer et al., 2007). MED28-specific knockdown resulted in up-regulation of several SMC-related genes and SMC phenotype, whereas ectopic expression of MED28 reversed the SMC morphology induced by MED28 knockdown (Beyer et al., 2007).
Angiogenesis: MED28 expression was increased by two-fold in human umbilical vein endothelial cells (HUVECs) treated with either tumor conditioned media or specific angiogenic factors (Liu et al., 2002). This observation suggests a role of MED28 in angiogenesis.
Cell migration: The role of MED28 in cell migration was demonstrated in both estrogen receptor (ER)-positive and negative human breast cancer cell lines (Huang et al., 2012; Lee et al., 2011). Ectopic expression of MED28 increased cell migration and invasion in MCF7 and MDA-MB-231 breast cancer cells (Huang et al., 2012; Lee et al., 2011). Investigation of the underlying mechanisms revealed that MED28 activates epidermal growth factor (EGF)-stimulated migration through induction of matrix metalloproteinase 9 (MMP9) in EGFR-overexpressing MDA-MB-231 cells (Lee et al., 2011). In addition, MED28 can also regulate cell migration through the mitogen-activated protein kinase kinase 1 (MAP2K1; MEK1)-dependent MMP2 activation, which is independent of EGF stimulation (Huang et al., 2012). These lines of evidence support the role of MED28 in cell migration, implying that MED28 might be responsible for cancer metastasis.
NCBI: 80306 MIM: 610311 HGNC: 24628 Ensembl: ENSG00000118579
dbSNP: 80306 ClinVar: 80306 TCGA: ENSG00000118579 COSMIC: MED28
Ming-Fen Lee ; Chun-Yin Huang
MED28 (mediator complex subunit 28)
Atlas Genet Cytogenet Oncol Haematol. 2012-07-01
Online version: http://atlasgeneticsoncology.org/gene/50131/gene-fusions-explorer/cancer-prone-explorer/meetings/