Skip to main content

Advertisement

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]
  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].
  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].
  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.
  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].