Illuminating the Dark: Highly Selective Inhibition of Serine/Threonine Kinase 17A with Pyrazolo[1,5-]pyrimidine-Based Macrocycles.

Serine/threonine kinase 17A (death-associated protein kinase-related apoptosis-inducing protein kinase 1─DRAK1) is a part of the death-associated protein kinase (DAPK) family and belongs to the so-called dark kinome. Thus, the current state of knowledge of the cellular function of DRAK1 and its involvement in pathophysiological processes is very limited. Recently, DRAK1 has been implicated in tumorigenesis of glioblastoma multiforme (GBM) and other cancers, but no selective inhibitors of DRAK1 are available yet.

Distinct contributions of DNA methylation and histone acetylation to the genomic occupancy of transcription factors.

Epigenetic modifications on chromatin play important roles in regulating gene expression. Although chromatin states are often governed by multilayered structure, how individual pathways contribute to gene expression remains poorly understood. For example, DNA methylation is known to regulate transcription factor binding but also to recruit methyl-CpG binding proteins that affect chromatin structure through the activity of histone deacetylase complexes (HDACs).

Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines.

Silencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome-wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies.

DNA methylation in germ cell tumour aetiology: current understanding and outstanding questions.

Germ cell tumours (GCTs) are a diverse group of neoplasms that can be histologically subclassified as either seminomatous or non-seminomatous. These two subtypes have distinct levels of differentiation and clinical characteristics, the non-seminomatous tumours being associated with poorer prognosis. In this article, we review how different patterns of aberrant DNA methylation relate to these subtypes.