Elk1 activation being hindered in this pathway, the SRE-driven gene regulation leads to increased vulnerability of neurons. Elk1 also inhibits transcription of presenilin 1 (PS1), which encodes a protein that is necessary for the last step of the sequential proteolytic processing of amyloid precursor protein (APP). APP makes variants of Aβ (Aβ42/43 polypeptide). Moreover, PS1 is genetically associated with most early-onset cases of familial Alzheimer's disease. These data emphasize the intriguing link between Aβ, Elk1, and PS1. Another condition associated with Elk1 is Down syndrome. Fetal and aged mice with this pathophysiological condition have shown a decrease in the activity of calcineurin, the major phosphatase for Elk1. These mice also have age-dependent changes in ERK activation. Moreover, expression of SUMO3, which represses Elk1 activity, increases in the adult Down syndrome patient. Therefore, Down syndrome is correlated with changes in ERK, calcineurin, and SUMO pathways, all of which act antagonistically on Elk1 activity. Elk1 also interacts with BRCA1 splice variants, namely BRCA1a and BRCA1b. This interaction enhances BRCA1-mediated growth suppression in breast cancer cells. Elk1 may be a downstream target of BRCA1 in its growth control pathway. Recent literature reveals that c-fos promoter activity is inhibited, while overexpression of BRCA1a/1b reduces MEK-induced activation of the SRE. These results show that one mechanism of growth and tumor suppression by BRCA1a/1b proteins acts through repression of the expression of Elk1 downstream target genes like Fos. Depression has been linked with Elk1. Decreased Erk-mediated Elk1 phosphorylation is observed in the hippocampus and prefrontal cortex of post-mortem brains of suicidal individuals. Imbalanced Erk signaling is correlated with depression and suicidal behavior. Future research will reveal the exact role of Elk1 in the pathophysiology of depression. References External links Transcription factors