POU3F2, also known as BRN2, is a transcription factor that h...

created [InstanceEdit:9858284] Rothfels, Karen, 2024-01-10
dbId 9858290
displayName POU3F2, also known as BRN2, is a transcription factor that h...
modified [InstanceEdit:9859417] Rothfels, Karen, 2024-01-19
schemaClass Summation
text POU3F2, also known as BRN2, is a transcription factor that has roles in neuronal development and plays roles in the development of the melanocyte lineage and in the progression of melanoma downstream of the WNT, MAPK and PI3K pathways (Goodall et al, 2004a; Goodall et al, 2004b; Bonvin et al, 2012; reviewed in Fane et al, 2019; Goding and Arnheiter, 2019; Cook et al, 2008). POU3F2 has been shown to bind directly to promoter elements upstream of the MITF gene by EMSA (Herbert et al, 2019; Goodall et al, 2008). In melanoma cells, POU3F2 has been reported as both an activator and a repressor of MITF expression (Wellbrock et al, 2008; Goodall et al, 2008). The ability of POU3F2 to bind DNA may depend in part on a conformational change in the N-terminal region in response to p38-dependent phosphorylation at residues S91 and S96, providing a link through p38 to the UV stress response (Herbert et al, 2019).
The relationship of POU3F2 and MITF expression appears to be somewhat context dependent. During melanogenesis, POU3F2 is expressed in neural crest precursor cells in a manner that depends on WNT, PI3K and MAPK signaling, but is not expressed in melanoblasts or in melanocytes that express MITF (Goodall et al, 2004a, Cook et al, 2003). During melanoma progression, POU3F2 and MITF are expressed in distinct subsets of cells within a tumor (Goodall et al, 2008, Thurber et al, 2011), possibly as the result of a negative feedback loop established through the MITF target miR-211 that downregulates POU3F2 levels (Boyle et al, 2011). POU3F2 expression has a role in driving invasion of melanoma cells, and the relative levels of MITF and POU3F2 may act to regulate the proliferative versus invasive properties of these cells (reviewed in Fane et al, 2019; Goding and Arnheiter et al, 2019).
In addition to its role at the promoter of the MITF gene, POU3F2 has also been implicated in the DNA damage response (DDR) pathway in melanoma cells by virtue of its interaction with DDR factors such as DNA-dependent protein kinases DNAPK and PRKDC, PARP1 and the Ku70/Ku80 dimer (Herbert et al, 2019). The interaction of POU3F2 and Ku70/80 dimer promotes resolution of DNA damage through the mutation prone non-homologous end-joining (NHEJ) pathway rather than through homologous recombination. In this way, POU3F2 may contribute to the high mutation burden of melanoma cell lines (Herbert et al, 2019; reviewed in Goding and Arnheiter, 2019; Fane et al, 2019).
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