Syndecan 1 is a
protein which in humans is encoded by the SDC1gene.[5][6] The protein is a transmembrane (type I)
heparan sulfateproteoglycan and is a member of the
syndecan proteoglycan family. The syndecan-1 protein functions as an
integral membrane protein and participates in
cell proliferation,
cell migration and
cell-matrix interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors and chemokines,[7] with binding largely via heparan sulfate chains. The syndecans mediate cell binding,
cell signaling, and
cytoskeletal organization and syndecan receptors are required for internalization of the
HIV-1tat protein.
Altered syndecan-1 expression has been detected in several different tumor types. Syndecan 1 can be a marker for
plasma cells.
Structure
The syndecan-1 core protein consists of an extracellular domain which can be substituted with heparan sulfate and
chondroitin sulfateglycosaminoglycan chains, a highly conserved transmembrane domain, and a highly conserved cytoplasmic domain, which contains two constant regions that are separated by a variable region.[8] The extracellular domain can be cleaved (shed) from the cell surface at a juxtamembrane site,[9] converting the membrane-bound proteoglycan into a paracrine effector molecule with roles in wound repair [10] and invasive growth of cancer cells.[11]
An exception is the prosecretory mitogen
lacritin that binds syndecan-1 only after heparanase modification.[12][13] Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial
heparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.[12] Three SDC1 elements are required. (1) The heparanase-exposed hydrophobic sequence GAGAL that promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix form and likely binds to the hydrophobic face. (2) Heparanase-cleaved heparan sulfate that is 3-O sulfated.[13] This likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix. (3) An N-terminal chondroitin sulfate chain that also likely binds to the cationic face. Point mutagenesis of lacritin has narrowed the ligation site.[13]
While several
transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.[14]
Altered syndecan-1 expression has been detected in several different tumor types.[23][24] In
breast cancer, syndecan-1 is up regulated and contributes to the
cancer stem cell phenotype, which is linked to increased resistance to
chemotherapy and radiation therapy [25][26][27]
It is a useful marker for
plasma cells,[29] but only if the cells tested are already known to be derived from blood.[30] For plasma cells, it usually stains intensely membranous, with or without associated diffuse weak cytoplasmic and/or Golgi staining.[31] Few cases show cytoplasmic granular staining, with or without associated Golgi staining.[31]
^Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (September 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2". Somatic Cell and Molecular Genetics. 16 (5): 501–505.
doi:
10.1007/BF01233200.
PMID2173154.
S2CID43270934.
^Bernfield M, Götte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M (1999). "Functions of cell surface heparan sulfate proteoglycans". Annual Review of Biochemistry. 68: 729–777.
doi:
10.1146/annurev.biochem.68.1.729.
PMID10872465.
^Hassan H, Greve B, Pavao MS, Kiesel L, Ibrahim SA, Götte M (May 2013). "Syndecan-1 modulates β-integrin-dependent and interleukin-6-dependent functions in breast cancer cell adhesion, migration, and resistance to irradiation". The FEBS Journal. 280 (10): 2216–2227.
doi:
10.1111/febs.12111.
PMID23289672.
S2CID19929711.
David G (1992). "Structural and Functional Diversity of the Heparan Sulfate Proteoglycans". Heparin and Related Polysaccharides. Advances in Experimental Medicine and Biology. Vol. 313. pp. 69–78.
doi:
10.1007/978-1-4899-2444-5_7.
ISBN978-1-4899-2446-9.
PMID1442271.
Vainio S, Jalkanen M, Bernfield M, Saxén L (August 1992). "Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney". Developmental Biology. 152 (2): 221–232.
doi:
10.1016/0012-1606(92)90130-9.
PMID1644217.
Kiefer MC, Ishihara M, Swiedler SJ, Crawford K, Stephans JC, Barr PJ (1992). "The molecular biology of heparan sulfate fibroblast growth factor receptors". Annals of the New York Academy of Sciences. 638: 167–176.
doi:
10.1111/j.1749-6632.1991.tb49027.x.
PMID1664683.
S2CID29216939.
Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (September 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2". Somatic Cell and Molecular Genetics. 16 (5): 501–505.
doi:
10.1007/BF01233200.
PMID2173154.
S2CID43270934.
Spring J, Goldberger OA, Jenkins NA, Gilbert DJ, Copeland NG, Bernfield M (June 1994). "Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family". Genomics. 21 (3): 597–601.
doi:
10.1006/geno.1994.1319.
PMID7959737.
Sneed TB, Stanley DJ, Young LA, Sanderson RD (February 1994). "Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells". Cellular Immunology. 153 (2): 456–467.
doi:
10.1006/cimm.1994.1042.
PMID8118875.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174.
doi:
10.1016/0378-1119(94)90802-8.
PMID8125298.
Albini A, Benelli R, Presta M, Rusnati M, Ziche M, Rubartelli A, et al. (January 1996). "HIV-tat protein is a heparin-binding angiogenic growth factor". Oncogene. 12 (2): 289–297.
PMID8570206.
Kaukonen J, Alanen-Kurki L, Jalkanen M, Palotie A (March 1997). "The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p". Human Genetics. 99 (3): 295–297.
doi:
10.1007/s004390050360.
PMID9050911.
S2CID30155082.
Syndecan 1 is a
protein which in humans is encoded by the SDC1gene.[5][6] The protein is a transmembrane (type I)
heparan sulfateproteoglycan and is a member of the
syndecan proteoglycan family. The syndecan-1 protein functions as an
integral membrane protein and participates in
cell proliferation,
cell migration and
cell-matrix interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors and chemokines,[7] with binding largely via heparan sulfate chains. The syndecans mediate cell binding,
cell signaling, and
cytoskeletal organization and syndecan receptors are required for internalization of the
HIV-1tat protein.
Altered syndecan-1 expression has been detected in several different tumor types. Syndecan 1 can be a marker for
plasma cells.
Structure
The syndecan-1 core protein consists of an extracellular domain which can be substituted with heparan sulfate and
chondroitin sulfateglycosaminoglycan chains, a highly conserved transmembrane domain, and a highly conserved cytoplasmic domain, which contains two constant regions that are separated by a variable region.[8] The extracellular domain can be cleaved (shed) from the cell surface at a juxtamembrane site,[9] converting the membrane-bound proteoglycan into a paracrine effector molecule with roles in wound repair [10] and invasive growth of cancer cells.[11]
An exception is the prosecretory mitogen
lacritin that binds syndecan-1 only after heparanase modification.[12][13] Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial
heparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.[12] Three SDC1 elements are required. (1) The heparanase-exposed hydrophobic sequence GAGAL that promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix form and likely binds to the hydrophobic face. (2) Heparanase-cleaved heparan sulfate that is 3-O sulfated.[13] This likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix. (3) An N-terminal chondroitin sulfate chain that also likely binds to the cationic face. Point mutagenesis of lacritin has narrowed the ligation site.[13]
While several
transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.[14]
Altered syndecan-1 expression has been detected in several different tumor types.[23][24] In
breast cancer, syndecan-1 is up regulated and contributes to the
cancer stem cell phenotype, which is linked to increased resistance to
chemotherapy and radiation therapy [25][26][27]
It is a useful marker for
plasma cells,[29] but only if the cells tested are already known to be derived from blood.[30] For plasma cells, it usually stains intensely membranous, with or without associated diffuse weak cytoplasmic and/or Golgi staining.[31] Few cases show cytoplasmic granular staining, with or without associated Golgi staining.[31]
^Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (September 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2". Somatic Cell and Molecular Genetics. 16 (5): 501–505.
doi:
10.1007/BF01233200.
PMID2173154.
S2CID43270934.
^Bernfield M, Götte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M (1999). "Functions of cell surface heparan sulfate proteoglycans". Annual Review of Biochemistry. 68: 729–777.
doi:
10.1146/annurev.biochem.68.1.729.
PMID10872465.
^Hassan H, Greve B, Pavao MS, Kiesel L, Ibrahim SA, Götte M (May 2013). "Syndecan-1 modulates β-integrin-dependent and interleukin-6-dependent functions in breast cancer cell adhesion, migration, and resistance to irradiation". The FEBS Journal. 280 (10): 2216–2227.
doi:
10.1111/febs.12111.
PMID23289672.
S2CID19929711.
David G (1992). "Structural and Functional Diversity of the Heparan Sulfate Proteoglycans". Heparin and Related Polysaccharides. Advances in Experimental Medicine and Biology. Vol. 313. pp. 69–78.
doi:
10.1007/978-1-4899-2444-5_7.
ISBN978-1-4899-2446-9.
PMID1442271.
Vainio S, Jalkanen M, Bernfield M, Saxén L (August 1992). "Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney". Developmental Biology. 152 (2): 221–232.
doi:
10.1016/0012-1606(92)90130-9.
PMID1644217.
Kiefer MC, Ishihara M, Swiedler SJ, Crawford K, Stephans JC, Barr PJ (1992). "The molecular biology of heparan sulfate fibroblast growth factor receptors". Annals of the New York Academy of Sciences. 638: 167–176.
doi:
10.1111/j.1749-6632.1991.tb49027.x.
PMID1664683.
S2CID29216939.
Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (September 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2". Somatic Cell and Molecular Genetics. 16 (5): 501–505.
doi:
10.1007/BF01233200.
PMID2173154.
S2CID43270934.
Spring J, Goldberger OA, Jenkins NA, Gilbert DJ, Copeland NG, Bernfield M (June 1994). "Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family". Genomics. 21 (3): 597–601.
doi:
10.1006/geno.1994.1319.
PMID7959737.
Sneed TB, Stanley DJ, Young LA, Sanderson RD (February 1994). "Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells". Cellular Immunology. 153 (2): 456–467.
doi:
10.1006/cimm.1994.1042.
PMID8118875.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174.
doi:
10.1016/0378-1119(94)90802-8.
PMID8125298.
Albini A, Benelli R, Presta M, Rusnati M, Ziche M, Rubartelli A, et al. (January 1996). "HIV-tat protein is a heparin-binding angiogenic growth factor". Oncogene. 12 (2): 289–297.
PMID8570206.
Kaukonen J, Alanen-Kurki L, Jalkanen M, Palotie A (March 1997). "The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p". Human Genetics. 99 (3): 295–297.
doi:
10.1007/s004390050360.
PMID9050911.
S2CID30155082.