Background: The inhibitor of apoptosis protein (IAP) family consists of an evolutionarily conserved group of apoptosis inhibitors containing a conserved 70 amino acid BIR (baculovirus inhibitor repeat) domain (1,2). Human members of this family include c-IAP1, c-IAP2, XIAP, survivin, livin, and NAIP. Overexpression of IAP family members, particularly survivin and livin, in cancer cell lines and primary tumors suggests an important role for these proteins in cancer progression (3-5). In general, the IAP proteins function through direct interactions to inhibit the activity of several caspases, including caspase-3, caspase-7, and caspase-9 (5,6). In addition, binding of IAP family members to the mitochondrial protein Smac blocks their interaction with caspase-9, thereby allowing the processing and activation of the caspase (2).
Background: YAP and TAZ (WWTR1) are transcriptional co-activators that play a central role in the Hippo Signaling pathway that regulates cell, tissue and organ growth. Under growth conditions, YAP and TAZ are translocated to the nucleus, where they interact with DNA-binding transcription factors (e.g., Transcriptional Enhanced Activation Domain [TEAD] proteins) to regulate the expression of genes that control fundamental aspects of cell function, such as proliferation and cell survival (1). A number of genes have been experimentally confirmed as targets of transcriptional regulation by YAP and TAZ. These include the extracellular matrix proteins CTGF, CYR61, and integrin β2 (2-4), the inhibitor of apoptosis protein (IAP) survivin (5), the mechano-sensitive nuclear envelope protein Lamin B2 (6), and the oncogenic receptor tyrosine kinase Axl (7).
Background: Distinct microglial activation states have been identified using RNA-seq data from a vast array of neurological disease and aging models. These activation states have been categorized into modules corresponding to proliferation, neurodegeneration, interferon-relation, LPS-relation, and many others (1). Previous work identifying markers of specific brain cell types using RNA-seq has shown HS1 and ASC/TMS1 to be useful and specific tools to study microglia (2). HS1 is a protein kinase substrate that is expressed only in tissues and cells of hematopoietic origin (3) and ASC/TMS1 has been found to be a critical component of inflammatory signaling where it associates with and activates caspase-1 in response to pro-inflammatory signals (4).