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Loss of sequences from human chromosome 10q has been associated with the progression of human cancers.  The gene DMBT1 was originally isolated based on its deletion in a medulloblastoma cell line.  DMBT1 is expressed with transcripts of 6.0, 7.5, and 8.0 kb in fetal lung and with one transcript of 8.0 kb in adult lung, although the 7.5 kb transcript has not been characterized.  The DMBT1 protein is a glycoprotein containing multiple scavenger receptor cysteine-rich (SRCR) domains separated by SRCR-interspersed domains (SID).  Transcript variant 2 (8.0 kb) has been shown to bind surfactant protein D independently of carbohydrate recognition.  This indicates that DMBT1 may not be a classical tumor suppressor gene, but rather play a role in the interaction of tumor cells and the immune system.<ref name="entrez">{{cite web | title = Entrez Gene: DMBT1 deleted in malignant brain tumors 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1755| accessdate = }}</ref>
Loss of sequences from human chromosome 10q has been associated with the progression of human cancers.  The gene DMBT1 was originally isolated based on its deletion in a medulloblastoma cell line.  DMBT1 is expressed with transcripts of 6.0, 7.5, and 8.0 kb in fetal lung and with one transcript of 8.0 kb in adult lung, although the 7.5 kb transcript has not been characterized.  The DMBT1 protein is a glycoprotein containing multiple scavenger receptor cysteine-rich (SRCR) domains separated by SRCR-interspersed domains (SID).  Transcript variant 2 (8.0 kb) has been shown to bind surfactant protein D independently of carbohydrate recognition.  This indicates that DMBT1 may not be a classical tumor suppressor gene, but rather play a role in the interaction of tumor cells and the immune system.<ref name="entrez">{{cite web | title = Entrez Gene: DMBT1 deleted in malignant brain tumors 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1755| accessdate = }}</ref>
== Pattern recognition and potential use of DMBT1 in nanomedicine ==
At epithelial barriers molecular pattern recognition mechanisms act as minesweepers against harmful environmental factors and thereby play a crucial role in the defense against invading bacterial and viral pathogens. However, it became evident that some of the proteins participating in these host defense processes may simultaneously function as regulators of tissue regeneration when in the extracellular matrix, thus coupling defense functions with regulation of stem cells. Although molecular pattern recognition has complex physiological roles and we just begin to understand its various functions, the simplicity of the underlying principles for recognition of specific classes of molecules may generate novel starting points for nanomedical approaches in drug delivery across epithelial barriers. The protein DMBT1, showed pattern recognition activity for poly-sulfated and poly-phosphorylated ligands, including nucleic acids, and the ability to aggregate ligands. This raises the interesting question in how far these properties can be utilized to assemble nucleic acidpeptide nano-complexes and whether this can be exploited to modulate the pharmacological properties of nucleic acids and/or for nucleic acid delivery to target cells <ref>{{Cite journal|last=Casella|first=Cinzia|last2=Tuttolomondo|first2=Martina|last3=Høilund-Carlsen|first3=Poul Flemming|last4=Mollenhauer|first4=Jan|date=2014-01-01|title=Natural pattern recognition mechanisms at epithelial barriers and potential use in nanomedicine|url=https://www.degruyter.com/view/j/ejnm.2014.6.issue-3/ejnm-2014-0020/ejnm-2014-0020.xml|journal=European Journal of Nanomedicine|language=en|volume=6|issue=3|doi=10.1515/ejnm-2014-0020|issn=1662-596X}}</ref> Recently, DMBT1-derived peptides have been successfully harnessed for siRNA intracellular delivery. <ref name=":0">{{Cite journal|last=Tuttolomondo|first=Martina|last2=Casella|first2=Cinzia|last3=Hansen|first3=Pernille Lund|last4=Polo|first4=Ester|last5=Herda|first5=Luciana M.|last6=Dawson|first6=Kenneth A.|last7=Ditzel|first7=Henrik J.|last8=Mollenhauer|first8=Jan|date=2017|title=Human DMBT1-Derived Cell-Penetrating Peptides for Intracellular siRNA Delivery|url=http://dx.doi.org/10.1016/j.omtn.2017.06.020|journal=Molecular Therapy - Nucleic Acids|volume=8|pages=264–276|doi=10.1016/j.omtn.2017.06.020|issn=2162-2531|via=}}</ref>


== Interactions ==
== Interactions ==


DMBT1 has been shown to [[Protein-protein interaction|interact]] with [[Surfactant protein D]].<ref name="pmid10101009">{{cite journal | vauthors = Tino MJ, Wright JR | title = Glycoprotein-340 binds surfactant protein-A (SP-A) and stimulates alveolar macrophage migration in an SP-A-independent manner | journal = Am. J. Respir. Cell Mol. Biol. | volume = 20 | issue = 4 | pages = 759–68 | year = 1999 | pmid = 10101009 | doi = 10.1165/ajrcmb.20.4.3439 }}</ref><ref name="pmid9153228">{{cite journal | vauthors = Holmskov U, Lawson P, Teisner B, Tornoe I, Willis AC, Morgan C, Koch C, Reid KB | title = Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule | journal = J. Biol. Chem. | volume = 272 | issue = 21 | pages = 13743–9 | year = 1997 | pmid = 9153228 | doi = 10.1074/jbc.272.21.13743 }}</ref>
DMBT1 has been shown to [[Protein-protein interaction|interact]] with [[Surfactant protein D]].<ref name="pmid10101009">{{cite journal | vauthors = Tino MJ, Wright JR | title = Glycoprotein-340 binds surfactant protein-A (SP-A) and stimulates alveolar macrophage migration in an SP-A-independent manner | journal = Am. J. Respir. Cell Mol. Biol. | volume = 20 | issue = 4 | pages = 759–68 | year = 1999 | pmid = 10101009 | doi = 10.1165/ajrcmb.20.4.3439 }}</ref><ref name="pmid9153228">{{cite journal | vauthors = Holmskov U, Lawson P, Teisner B, Tornoe I, Willis AC, Morgan C, Koch C, Reid KB | title = Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule | journal = J. Biol. Chem. | volume = 272 | issue = 21 | pages = 13743–9 | year = 1997 | pmid = 9153228 | doi = 10.1074/jbc.272.21.13743 }}</ref> DMBT1-derived peptides also interacts with nucleic acids. <ref name=":0" />


== References ==
== References ==

Latest revision as of 19:18, 25 September 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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Deleted in malignant brain tumors 1 protein is a protein that in humans is encoded by the DMBT1 gene.[1][2]

Function

Loss of sequences from human chromosome 10q has been associated with the progression of human cancers. The gene DMBT1 was originally isolated based on its deletion in a medulloblastoma cell line. DMBT1 is expressed with transcripts of 6.0, 7.5, and 8.0 kb in fetal lung and with one transcript of 8.0 kb in adult lung, although the 7.5 kb transcript has not been characterized. The DMBT1 protein is a glycoprotein containing multiple scavenger receptor cysteine-rich (SRCR) domains separated by SRCR-interspersed domains (SID). Transcript variant 2 (8.0 kb) has been shown to bind surfactant protein D independently of carbohydrate recognition. This indicates that DMBT1 may not be a classical tumor suppressor gene, but rather play a role in the interaction of tumor cells and the immune system.[3]

Pattern recognition and potential use of DMBT1 in nanomedicine

At epithelial barriers molecular pattern recognition mechanisms act as minesweepers against harmful environmental factors and thereby play a crucial role in the defense against invading bacterial and viral pathogens. However, it became evident that some of the proteins participating in these host defense processes may simultaneously function as regulators of tissue regeneration when in the extracellular matrix, thus coupling defense functions with regulation of stem cells. Although molecular pattern recognition has complex physiological roles and we just begin to understand its various functions, the simplicity of the underlying principles for recognition of specific classes of molecules may generate novel starting points for nanomedical approaches in drug delivery across epithelial barriers. The protein DMBT1, showed pattern recognition activity for poly-sulfated and poly-phosphorylated ligands, including nucleic acids, and the ability to aggregate ligands. This raises the interesting question in how far these properties can be utilized to assemble nucleic acidpeptide nano-complexes and whether this can be exploited to modulate the pharmacological properties of nucleic acids and/or for nucleic acid delivery to target cells [4] Recently, DMBT1-derived peptides have been successfully harnessed for siRNA intracellular delivery. [5]

Interactions

DMBT1 has been shown to interact with Surfactant protein D.[6][7] DMBT1-derived peptides also interacts with nucleic acids. [5]

References

  1. ↑ Mollenhauer J, Wiemann S, Scheurlen W, Korn B, Hayashi Y, Wilgenbus KK, von Deimling A, Poustka A (Oct 1997). "DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours". Nat. Genet. 17 (1): 32–9. doi:10.1038/ng0997-32. PMID 9288095.
  2. ↑ Rosenstiel P, Sina C, End C, Renner M, Lyer S, Till A, Hellmig S, Nikolaus S, Fölsch UR, Helmke B, Autschbach F, Schirmacher P, Kioschis P, Hafner M, Poustka A, Mollenhauer J, Schreiber S (Jun 2007). "Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates bacterial recognition and invasion". J. Immunol. 178 (12): 8203–11. doi:10.4049/jimmunol.178.12.8203. PMID 17548659.
  3. ↑ "Entrez Gene: DMBT1 deleted in malignant brain tumors 1".
  4. ↑ Casella, Cinzia; Tuttolomondo, Martina; Høilund-Carlsen, Poul Flemming; Mollenhauer, Jan (2014-01-01). "Natural pattern recognition mechanisms at epithelial barriers and potential use in nanomedicine". European Journal of Nanomedicine. 6 (3). doi:10.1515/ejnm-2014-0020. ISSN 1662-596X.
  5. ↑ 5.0 5.1 Tuttolomondo, Martina; Casella, Cinzia; Hansen, Pernille Lund; Polo, Ester; Herda, Luciana M.; Dawson, Kenneth A.; Ditzel, Henrik J.; Mollenhauer, Jan (2017). "Human DMBT1-Derived Cell-Penetrating Peptides for Intracellular siRNA Delivery". Molecular Therapy - Nucleic Acids. 8: 264–276. doi:10.1016/j.omtn.2017.06.020. ISSN 2162-2531.
  6. ↑ Tino MJ, Wright JR (1999). "Glycoprotein-340 binds surfactant protein-A (SP-A) and stimulates alveolar macrophage migration in an SP-A-independent manner". Am. J. Respir. Cell Mol. Biol. 20 (4): 759–68. doi:10.1165/ajrcmb.20.4.3439. PMID 10101009.
  7. ↑ Holmskov U, Lawson P, Teisner B, Tornoe I, Willis AC, Morgan C, Koch C, Reid KB (1997). "Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule". J. Biol. Chem. 272 (21): 13743–9. doi:10.1074/jbc.272.21.13743. PMID 9153228.

Further reading


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