Small Kinetochore-Associated Protein (SKAP)/Kinastrin is a multifunctional protein with proposed roles in mitosis, apoptosis and cell migration. Exact mechanisms underlying its activities in these cellular processes are not completely understood. SKAP is predicted to have different isoforms, however, previous studies did not differentiate between them. Since distinct molecular architectures of protein isoforms often influence their localization and functions, this study aimed to examine the expression profile and functional differences between SKAP isoforms in human and mouse. Analyses of various human tissues and cells of different origin by RT-PCR, and by Western blotting and immunocytochemistry applying newly generated anti-SKAP monoclonal antibodies revealed that human SKAP exists in two protein isoforms: ubiquitously expressed SKAP16 and testis/sperm-specific SKAP1. In mouse, SKAP1 expression is detectable in testis at 4 weeks postnatally, when the first wave of spermatogenesis in mice is complete and the elongated spermatids are present in the testes. Furthermore, we identified Pontin as a new SKAP1 interaction partner. SKAP1 and Pontin co-localized in the flagellar region of human sperm suggesting a functional relevance for SKAP1-Pontin interaction in sperm motility. Since most previous studies on SKAP were performed with the testis-specific isoform SKAP1, our findings provide a new basis for future studies on the role of SKAP in both human somatic cells and male germ cells, including studies on male fertility.
aktoren von Bedeutung, da diese Faktoren für den Hauptanteil der transkriptionellen Aktivität von YAP/TAZ verantwortlich sind. Der Hippo-Signalweg kann durch eine Vielzahl von Stimuli aktiviert und moduliert werden, wobei die genaue Entschlüsselung dieser vorgeschalteten Mechanismen noch Gegenstand intensiver Forschung ist. YAP/TAZ in der Regeneration Aufgrund des starken Wachstumsphänotyps nach deregulierter Aktivität des Hippo-Signalweges in D. melanogaster haben sich zunächst viele Forschungsarbeiten auf die Rolle dieses Signalweges in der Tumorgenese MARIE TOLLOT, ANITA CINDRIC VRANESIC, BJÖRN VON EYSS LEIBNIZ-INSTITUT FÜR ALTERNSFORSCHUNG-FRITZ-LIPMANN-INSTITUT (FLI), JENA The Hippo signalling pathway is a highly conserved regulator of tissue homeostasis and regeneration. Numerous studies in mouse and human have associated aberrant Hippo pathway activity with cancer development. YAP-the main downstream Hippo pathway effectorcan function both as an oncoprotein and a tumor suppressor depending on the cellular context. We recently identifi ed TRPS1 as a novel repressor of YAP activity.
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