title: Heparan sulfate in the nucleus and its control of cellular functions.
abstract: Heparan sulfate proteoglycans (HSPG) are present on the cell surface, within the extracellular matrix, and as soluble molecules in tissues and blood. HSPGs are known to regulate a wide range of cellular functions predominantly by serving as co-receptors for growth factors, chemokines, and other regulatory proteins that control inflammation, wound healing and tumorigenesis. Several studies have demonstrated the presence of heparan sulfate (HS) or HSPGs in the cell nucleus, but little attention has been focused on their role there. However, evidence is mounting that nuclear HS and HSPGs have important regulatory functions that impact the cell cycle, proliferation, transcription and transport of cargo to the nucleus. The discovery of proteoglycans in the nucleus extends the list of "non-traditional nuclear proteins" that includes, for example, cytoskeletal proteins such as actin and tubulin, and growth factors and their receptors. In this review we discuss the discovery and fascinating roles of HS and HSPGs in the nucleus and propose a number of key questions that remain to be addressed.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Stewart
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: sanderson@uab.edu.
authors.forename: Ralph D
authors.initials: RD
authors.lastname: Sanderson
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D002468:Cell Physiological Phenomena / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans
chemical_list: D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate
keywords: Chromatin modification; Nuclear localization; Proliferation; Proteoglycan; Syndecan-1; Transcription