14-3-3s are a family of adaptor proteins with a wide range of roles in cell signaling. Although they are primarily localized within the cytosol, 14-3-3s are also known to be present in the extracellular environment. Externalization of 14-3-3 can occur as a result of cell death or physiologically via release in exosomes. Interesting biological activities with relevance for tissue homeostasis and disease are now being described for extracellular 14-3-3s. Moreover, aminopeptidase N (APN) has been identified as a cell surface receptor for 14-3-3s. Here we review the array of bioactivities that have been ascribed to extracellular 14-3-3s and discuss applications as biomarkers and as targets for drug development.
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http://dx.doi.org/10.1016/j.cellsig.2016.12.007 | DOI Listing |
Cyclin F, a non-canonical member of the cyclin protein family, plays a critical role in regulating the precise transitions of cell-cycle events. Unlike canonical cyclins, which bind and activate cyclin-dependent kinases (CDKs), Cyclin F functions as a substrate receptor protein within the Skp1-Cullin-F box (SCF) E3 ubiquitin ligase complex, enabling the ubiquitylation of target proteins. The structural features that distinguish Cyclin F as a ligase adaptor and the mechanisms underlying its selective substrate recruitment over Cyclin A, which functions in complex with CDK2 at a similar time in the cell cycle, remain largely unexplored.
View Article and Find Full Text PDFThe folded auto-inhibited state of kinesin-1 is stabilized by multiple weak interactions and binds weakly to microtubules. Here we investigate the extent to which homodimeric kinesin-1 lacking light chains is activated by the dynein activating adaptor BicD. We show that one or two kinesins can bind to the central region of BicD (CC2), a region distinct from that which binds dynein-dynactin (CC1) and cargo-adaptor proteins (CC3).
View Article and Find Full Text PDFCytoplasmic dynein is an essential microtubule motor protein that powers organelle transport and mitotic spindle assembly. Its activity depends on dynein-dynactin-cargo adaptor complexes, such as dynein-dynactin-BicD2 (DDB), which typically function with two dynein motors. We show that mechanical tension recruits a third dynein motor via an auxiliary BicD adaptor binding the light intermediate chain of the third dynein, stabilizing multi-dynein assemblies and enhancing force generation.
View Article and Find Full Text PDFWorld J Stem Cells
January 2025
Department of Anatomy and Cell Biology, College of Medicine, Chung-Ang University, Seoul 06974, South Korea.
Background: Human mesenchymal stromal cells (MSCs) possess regenerative potential due to pluripotency and paracrine functions. However, their stemness and immunomodulatory capabilities are sub-optimal in conventional two-dimensional (2D) culture.
Aim: To enhance the efficiency and therapeutic efficacy of MSCs, an -like 3D culture condition was applied.
Indiana Univ J Undergrad Res
June 2024
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine.
Angiomotins (Amots) are a family of adaptor proteins with important roles in cell growth, migration, and proliferation. The Amot coiled-coil homology (ACCH) domain has a high affinity for non-phosphorylated and mono-phosphorylated phosphatidylinositol which provides specificity in the membrane association. The membrane specificity is linked with targeting and recycling of the membrane protein to maintain normal cell phenotypes and function.
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