Heparan sulfate in the nucleus and its control of cellular functions

Matrix Biol. 2014 Apr:35:56-9. doi: 10.1016/j.matbio.2013.10.009. Epub 2013 Dec 3.

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.

Keywords: Chromatin modification; Nuclear localization; Proliferation; Proteoglycan; Syndecan-1; Transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Animals
  • Cell Cycle / physiology
  • Cell Nucleus / metabolism*
  • Cell Physiological Phenomena / physiology*
  • Cell Proliferation / physiology
  • Chromatin Assembly and Disassembly / physiology
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation / physiology*
  • Heparan Sulfate Proteoglycans / metabolism*
  • Heparitin Sulfate / metabolism*
  • Humans

Substances

  • Heparan Sulfate Proteoglycans
  • Heparitin Sulfate