The Salvador-Warts-Hippo (Hippo) pathway is an evolutionarily conserved regulator of organ growth and cell fate. It performs these functions in epithelial and neural tissues of both insects and mammals, as well as in mammalian organs such as the liver and heart. Despite rapid advances in Hippo pathway research, a definitive role for this pathway in hematopoiesis has remained enigmatic.
View Article and Find Full Text PDFAim: Influenza virus remains a major threat, with outbreaks continuing to occur. Few treatment options are available and drug resistance can emerge rapidly. New drugs that can quickly be adapted to virus mutations are needed.
View Article and Find Full Text PDFThe Salvador-Warts-Hippo (SWH) pathway is an important regulator of tissue growth that is frequently subverted in human cancer. The key oncoprotein of the SWH pathway is the transcriptional co-activator, Yes-associated protein (YAP). YAP promotes tissue growth and transformation of cultured cells by interacting with transcriptional regulatory proteins via its WW domains, or, in the case of the TEAD1-4 transcription factors, an N-terminal binding domain.
View Article and Find Full Text PDFBackground: Epithelial neoplasias are associated with alterations in cell polarity and excessive cell proliferation, yet how these neoplastic properties are related to one another is still poorly understood. The study of Drosophila genes that function as neoplastic tumor suppressors by regulating both of these properties has significant potential to clarify this relationship.
Results: Here we show in Drosophila that loss of Scribbled (Scrib), a cell polarity regulator and neoplastic tumor suppressor, results in impaired Hippo pathway signaling in the epithelial tissues of both the eye and wing imaginal disc.
During tissue regeneration, cell proliferation replaces missing structures to restore organ function. Regenerative potential differs greatly between organs and organisms; for example some amphibians can regrow entire limbs whereas mammals cannot. The process of regeneration relies on several signaling pathways that control developmental tissue growth, and implies the existence of organ size-control checkpoints that regulate both developmental, and regenerative, growth.
View Article and Find Full Text PDFThe newly discovered Salvador-Warts-Hippo (SWH) pathway is a key regulator of tissue growth during both development and disease. The first identified components of this pathway represent core downstream effector proteins: the kinases Warts and Hippo; the adaptor proteins Salvador and Mats; and the transcriptional co-activator Yorkie. More recently, a surprising number of proteins have been implicated as upstream regulators of the SWH pathway, including: the planar cell polarity cadherins Fat and Dachsous; the FERM-domain proteins Expanded and Merlin; the WW-domain protein Kibra; the Ras-association family protein dRASSF; and the apicobasal polarity proteins lethal giant larvae, atypical protein kinase C and Crumbs.
View Article and Find Full Text PDFBackground: How epithelial cells adopt their particular polarised forms is poorly understood. In a screen for genes regulating epithelial morphology in Drosophila, we identified sds22, a conserved gene previously characterised in yeast.
Results: In the columnar epithelia of imaginal discs or follicle cells, mutation of sds22 causes contraction of cells along their apical-basal axis, resulting in a more cuboidal morphology.