Androgen receptor (AR) transcriptional activity significantly influences prostate cancer (PCa) progression. In addition to ligand stimulation, AR transcriptional activity is also influenced by a variety of post-translational modifications (PTMs). A number of oncogenes and tumor suppressors have been observed leveraging PTMs to influence AR activity.
View Article and Find Full Text PDFAlthough mutations in have long been known to cause autosomal recessive Weill-Marchesani Syndrome which is characterized by short stature and ocular abnormalities, more recent work has shown that certain mutations in cause glaucoma in dogs. In humans, glaucoma is the leading cause of irreversible vision loss that affects tens of millions of people world-wide. Vision loss in glaucoma is a result of neurodegeneration of retinal ganglion cells that form the inner-most layer of the retina and whose axons form the optic nerve which relays visual information to the brain.
View Article and Find Full Text PDFThe process that partitions the nascent vertebrate central nervous system into forebrain, midbrain, hindbrain, and spinal cord after neural induction is of fundamental interest in developmental biology, and is known to be dependent on Wnt/β-catenin signaling at multiple steps. Neural induction specifies neural ectoderm with forebrain character that is subsequently posteriorized by graded Wnt signaling: embryological and mutant analyses have shown that progressively higher levels of Wnt signaling induce progressively more posterior fates. However, the mechanistic link between Wnt signaling and the molecular subdivision of the neural ectoderm into distinct domains in the anteroposterior (AP) axis is still not clear.
View Article and Find Full Text PDFThe establishment of anteroposterior identity in the vertebrate neural plate has been a subject of investigation for decades, but molecular explanations of posteriorization were only revealed beginning in the late 1980s. A model has emerged from several key studies that identifies Wnt signaling as a key posteriorizing agent, which evidence suggests specifies anteroposterior fates in a concentration-dependent manner. In this review, we consider the historical context of posteriorization studies and evaluate models for Wnt-dependent posteriorization.
View Article and Find Full Text PDFwnt8a Is essential for normal patterning during vertebrate embryonic development, and either gain or loss-of-function gene dysregulation results in severe axis malformations. The zebrafish wnt8a locus is structured such that transcripts may possess two regulatory 3' untranslated regions (UTRs), raising the possibility of post-transcriptional regulation as an important mode of wnt8a signaling control. To determine whether both UTRs contribute to post-transcriptional wnt8a gene regulation, each UTR (UTR1 and UTR2) was tested in transient and transgenic reporter assays.
View Article and Find Full Text PDF