PRDM16 (PR domain containing 16)

1p36.32

11 splice variants

1276 amino acids and smaller proteins. Contains a N-term PR domain; 7 Zinc fingers, a proline-rich domain, and 3 Zinc fingers in the C-term. Binds DNA. Transcription activator; PRDM16 has an intrinsic histone methyltransferase activity. PRDM16 forms a transcriptional complex with CEBPB. PRDM16 plays a downstream regulatory role in mediating TGFB signaling (Bjork et al., 2010). PRDM16 induces brown fat determination and differentiation. PRDM16 is expressed selectively in the earliest stem and progenitor hematopoietic cells, and is required for the maintenance of the hematopoietic stem cell pool during development. PRDM16 is also required for survival, cell-cycle regulation and self-renewal in neural stem cells (Chuikov et al., 2010; Kajimura et al., 2010; Aguilo et al., 2011; Chi and Cohen, 2016).

DUSP10 (dual specificity phosphatase 10)

1q41

482 amino acids. DUSP10 is a MAP kinase phosphatase. DUSP10 inactivate p38MAPK signaling by dephosphorylation. Activation/phosphorylation of the p38MAPK pathway inhibits tumor formation (the p38MAPK subfamily is composed by four members: MAPK11, MAPK12, MAPK13 and MAPK14 ). DUSP10 mRNA levels were lower in prostate cell lines derived from malignant tumor (Nonn L, 2011). High DUSP10 expression in colorectal cancer was found associated with improvement in survival. DUSP10 negatively regulates intestinal epithelial cell growth and acts as a suppressor for colorectal cancer (Png et al., 2016). DUSP10 polymorphisms influence the risk of developing colorectal cancer. DUSP10 was found expressed in meningiomas of all grades. DUSP10 expression with deactivation of p38MAPK may contribute to the pathogenesis of meningiomas (Johnson et al., 2016). AGR2, a protein known to be overexpressed in various human cancers and to provide a poor prognosis, up-regulates DUSP10 which subsequently inhibits p38MAPK, prevents TP53 activation by phosphorylation, and provides a poor prognosis in ER+breast cancer (Hrstka et al., 2016). mTORC2 (MTOR protein complex 2) binds and phosphorylates DUSP10, which blocks DUSP10 turnover resulting in inactivation of p38MAPK signaling. DUSP10 protein levels and phosphorylation is increased inglioblastoma multiforme tumors (Benavides-Serrato et al., 2014). MIR92A/DUSP10/JNK signaling: MIR92A targets DUSP10 (DUSP10 inhibits JKN signaling (MAPK8, MAPK9 and MAPK10, also called JNK1,2,3) to promote JNK signaling, which promotes pancreatic cancer cell proliferation. (He et al., 2014).