Table 3 Potential modulators of STAT1 activity detected by Mimosa using the known STAT1 targets and gene expression data from normal B cell and B cell cancers.
From: Mimosa: Mixture model of co-expression to detect modulators of regulatory interaction
Gene Name | Evidence |
|---|---|
Refseq Id | [Pubmed Id for the references are provided in square brackets] |
| Â | Modifying Enzymes |
GRK5 NM005308 | A Ser/Ther protein kinase that functions upstream of the JAK-STAT signal transduction pathway according to the KEGG pathway database http://www.genome.jp/kegg. |
UBE21 NM194261 | An E2 SUMO-conjugating enzyme implicated in SUMOylation of STAT1 in conjunction with PIAS1 [12855578, 12764129]. |
DUSP1 NM004417 | A dual specificity protein phosphatase. STAT1 is known to be primarily regulated by reversible tyrosine phosphorylation. DUSP1 has been shown to function in a JAK2-dependent manner [14551204] and the members of the JAK family are the canonical regulators of STATs, thus suggesting DUSP1 as a potential upstream modulator of STAT1. |
SIK1 NM173354 | A Ser/Thr kinase that negatively regulates the TGF-β pathway [18725536]. IFN-γ signaling is mediated via STAT1, while TGF-β and IFN-γ pathways are known to be directly antagonistic to each other [17116388], thus suggesting a role for SIK1 modulation of STAT1 in pathway cross-talk. |
INPP1 NM002194 | A phosphatase functioning upstream of major kinases such as AKT/PKB (KEGG pathway), which are known to mediate apoptotic signaling in B cells [17928528]. |
| Â | Receptors |
CD69 NM001781 | An early activation antigen functioning downstream of IFN-γ [12718936], and STAT1 activation is known to be interferon-responsive. |
LGALS8 NM201543 | Modulates cellular growth through up-regulation of p21 [15753078], which in turn is regulated by the STAT1 homolog STAT5A [12393707]. |
SELL NM000655 | Belongs to a family of adhesion/homing receptors which play important roles in leukocyte-endothelial cell interaction [12370391], while STAT1 also plays a crucial role in leukocyte-infiltration into the liver in T cell hepatitis [15246962]. |
| Â | Transcription factors and co-factors |
DIP NM198057 | Glucocorticoid-induced leucine zipper (GILZ) interacts with NF-kappaB [17169985] which is known to play a key role in B cell function. |
IRF7 NM004031 | An interferon regulatory factor 7, belonging to the same TF family as two known STAT1 co-factors, IRF-1 and IRF8 [18929502]. |
POLR2J NM006234 | Co-induced with STAT3 by HIV-1 gp120 [12089333]. |
POLR2J2 NM032959 | Related to POLR2J. |
ZNHIT3 NM004773 | A zinc finger transcription factor known to be a HNF-4α co-activator [11916906]. However, we did not find a potential link with STAT1. |
| Â | Other Immune Related Genes |
ADRM1 NM007002 | A proteasomal ubiquitin receptor whose expression has been shown to be induced by IFN-γ [8033103]. STAT1 activity is known to be modulated by ubiquitin-dependent protein degradation [18378670]. |
PSMD9 NM002813 | A 26S proteasome non-ATPase regulatory subunit involved in the processing of class I MHC peptides [8811196]. |
IFITM-1,2,3 NM003641 NM006435 NM021034 | Interferon-induced transmembrane proteins. These may be involved in STAT1 modulation, or they may be downstream of a pathway, most likely IFN-γ, which modulates STAT1 activity. |
HLA-A,C,E,F,G,L NM002116 NM002117 NM005516 NM018950 NM002127 NM001004349 | MHC class I genes. The function of this class of genes is well-characterized as cell-surface antigen presenters, and it is difficult to imagine how these genes might function upstream of STAT1. A more likely explanation is that they are activated downstream of, or in parallel to, STAT1 by another gene which also functions as a STAT1 modulator or co-factor. It is particularly striking that all of these genes belong to MHC class I, and none in MHC class II, which are known to be regulated by STAT1 [18929502]. |