Methods for Studying TGF-β Family Signaling in Development and Disease

TOPICAL COLLECTIONS

Guest Editors

Peter ten Dijke

Leiden University Medical Center, Dept. Cell and Chemical Biology

Peter ten Dijke received his PhD degree in 1991 from Wageningen University, The Netherlands based on his research on the identification of the third isoform of TGF-β performed at Oncogene Science, Inc., New York, USA. He did his postgraduate studies at the Ludwig Institute for Cancer Research (LICR), Uppsala, Sweden. In 1994, he became group leader at LICR, and in 1999 he moved to the Netherlands Cancer Institute, Amsterdam, The Netherlands. In 2005 he moved to the Leiden University Medical Center, Leiden, The Netherlands, and is currently a professor of molecular cell biology at Leiden University. His laboratory studies the molecular mechanisms by which TGF-β family members elicit their cellular effects via (co)receptors and intracellular SMAD effectors, and how subverted TGF-b family signaling is involved in cancer, vascular, and bone diseases.

Sijia Liu

Leiden University Medical Center

Sijia Liu performed her PhD studies in cell biology at Leiden University Medical Center under supervision of Prof. Peter ten Dijke. Her research focused on TGF-β signaling in cancer progression. She identified deubiquitinating enzyme UCHL1 as a candidate oncoprotein that promotes TGF-β-induced triple-negative breast cancer (TNBC) metastasis. She currently investigates a selective UCHL1 activity inhibitor for its drug potential for TNBC therapy and develops a cell permeable fluorescent activity-based probe to monitor UCHL1 activity in vivo.

Collection Overview

The transforming growth factor-β (TGF-β) family of growth and differentiation factors are pleiotropic cytokines that elicit a broad spectrum of cellular effects on many different cell types. They perform critical roles in embryogenesis and maintaining tissue homeostasis. Perturbation in TGF-β family signaling has been implicated in multiple developmental disorders and diseases, including cancer, fibrosis, and musculoskeletal and cardiovascular diseases. TGF-β family members signal via specific cell surface TGF-β type I and type II receptors that are endowed with serine/threonine kinase activity. Upon ligand-induced type I and type II heteromeric complex formation, the type II kinase phosphorylates type I on specific serine and threonine residues. The activated type I receptor subsequently initiates intracellular signaling by phosphorylating intracellular effector proteins of which the SMAD proteins have a key role. When receptor regulated SMADs are phosphorylated at their carboxy terminus they can form heteromeric complexes with SMAD4, which can translocate to the nucleus where they act as transcription factors to regulate target gene expression and biological responses. This collection is open for contributions on techniques to investigate TGF-β signaling and various biological responses, including biochemical methods to investigate the stability, localization, and function of TGF-β family signaling components, cellular responses on migration and differentiation, zebrafish and Xenopus development, and imaging of metastatic dissemination in mice. The contributions will include introductions to the topics, example experimental results and discussion, and provide detailed step by step protocols and lists of reagents that allow other researchers to implement these protocols in their own laboratories. In addition, troubleshooting help sections are included.