Biology:Dipeptidyl peptidase-4

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Short description: Mammalian protein found in Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Dipeptidyl peptidase-4 (DPP4 or DPPIV), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) is a protein that, in humans, is encoded by the DPP4 gene.[1] DPP4 is related to FAP, DPP8, and DPP9. The enzyme was discovered in 1966 by Hopsu-Havu and Glenner,[2] and as a result of various studies on chemism, was called dipeptidyl peptidase IV [DP IV].

Function

The protein encoded by the DPP4 gene is an enzyme expressed on the surface of most cell types and is associated with immune regulation, signal transduction, and apoptosis. It is a type II transmembrane glycoprotein, but a soluble form, which lacks the intracellular and transmembrane part, is present in blood plasma and various body fluids. DPP-4 is a serine exopeptidase that cleaves X-proline or X-alanine dipeptides from the N-terminus of polypeptides. Peptide bonds involving the cyclic amino acid proline cannot be cleaved by the majority of proteases and an N-terminal X-proline "shields" various biopeptides.[3] Extracellular proline-specific proteases therefore play an important role in the regulation of these biopeptides.

DPP-4 is known to cleave a broad range of substrates including growth factors, chemokines, neuropeptides, and vasoactive peptides.[4][5] The cleaved substrates lose their biological activity in the majority of cases, but in the case of the chemokine RANTES and neuropeptide Y, DPP-4 mediated cleavage leads to a shift in the receptor subtype binding.[4]

DPP4 plays a major role in glucose metabolism. It is responsible for the degradation of incretins such as GLP-1.[6] Furthermore, it appears to work as a suppressor in the development of some tumors.[7][8][9][10]

DPP-4 also binds the enzyme adenosine deaminase specifically and with high affinity. The significance of this interaction has yet to be established.

Animal studies

Animal studies suggest its pathogenetic role in development of fibrosis of various organs, such as liver and kidney.[11][12]

Clinical significance

CD26/DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum increased in some neoplasms and decreased in others.[13]

A class of oral hypoglycemics called dipeptidyl peptidase-4 inhibitors works by inhibiting the action of this enzyme, thereby prolonging incretin effect in vivo.[14]

Middle East respiratory syndrome coronavirus has been found to bind to DPP4. It is found on the surface of cells in the airways (such as the lungs) and kidneys. Scientists may be able to use this to their advantage by blocking the virus's entry into the cell.[15]

DPP4,[16] or its Mycobacterial homologue MtDPP,[17] might play a role in the pathogenesis of tuberculosis via cleavage of the chemokine C-X-C motif chemokine ligand 10 (CXCL10).

See also

  • Development of dipeptidyl peptidase-4 inhibitors
  • Berberine

References

  1. ↑ "Direct association of adenosine deaminase with a T cell activation antigen, CD26". Science 261 (5120): 466–9. July 1993. doi:10.1126/science.8101391. PMID 8101391. Bibcode: 1993Sci...261..466K. 
  2. ↑ "A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-beta-naphthylamide". Histochemie. Histochemistry. Histochimie 7 (3): 197–201. 1966. doi:10.1007/bf00577838. PMID 5959122. 
  3. ↑ "Proline motifs in peptides and their biological processing". FASEB Journal 9 (9): 736–44. June 1995. doi:10.1096/fasebj.9.9.7601338. PMID 7601338. 
  4. ↑ 4.0 4.1 "Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory peptides". Regulatory Peptides 85 (1): 9–24. November 1999. doi:10.1016/S0167-0115(99)00089-0. PMID 10588446. 
  5. ↑ "Biochemical properties of recombinant prolyl dipeptidases DPP-IV and DPP8". Dipeptidyl Aminopeptidases. Advances in Experimental Medicine and Biology. 575. 2006. pp. 27–32. doi:10.1007/0-387-32824-6_3. ISBN 978-0-387-29058-4. 
  6. ↑ "DPP-4 inhibitors and their potential role in the management of type 2 diabetes". International Journal of Clinical Practice 60 (11): 1454–70. November 2006. doi:10.1111/j.1742-1241.2006.01178.x. PMID 17073841. 
  7. ↑ "CD26/dipeptidyl peptidase IV and its role in cancer". Histology and Histopathology 19 (4): 1345–51. October 2004. doi:10.14670/HH-19.1345. PMID 15375776. 
  8. ↑ "DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells". Regulatory Peptides 137 (3): 147–55. December 2006. doi:10.1016/j.regpep.2006.07.003. PMID 16908079. 
  9. ↑ "Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway". Cancer Research 65 (4): 1325–34. February 2005. doi:10.1158/0008-5472.CAN-04-1852. PMID 15735018. 
  10. ↑ "Dipeptidyl peptidase IV activity and/or structure homologues (DASH) and their substrates in cancer". The International Journal of Biochemistry & Cell Biology 36 (3): 408–21. March 2004. doi:10.1016/S1357-2725(03)00262-0. PMID 14687920. 
  11. ↑ "Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats". Journal of Gastroenterology 49 (3): 481–91. March 2014. doi:10.1007/s00535-013-0783-4. PMID 23475323. 
  12. ↑ "Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction". Laboratory Investigation; A Journal of Technical Methods and Pathology 94 (6): 598–607. June 2014. doi:10.1038/labinvest.2014.50. PMID 24687121. 
  13. ↑ "The role of CD26/dipeptidyl peptidase IV in cancer". Frontiers in Bioscience 13 (13): 1634–45. January 2008. doi:10.2741/2787. PMID 17981655. http://www.bioscience.org/2008/v13/af/2787/fulltext.htm. 
  14. ↑ "Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus". Current Opinion in Endocrinology, Diabetes and Obesity 14 (2): 98–107. April 2007. doi:10.1097/MED.0b013e3280a02f65. PMID 17940427. 
  15. ↑ "Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC". Nature 495 (7440): 251–4. March 2013. doi:10.1038/nature12005. PMID 23486063. Bibcode: 2013Natur.495..251R. 
  16. ↑ "Interplay of DDP4 and IP-10 as a Potential Mechanism for Cell Recruitment to Tuberculosis Lesions". Front Immunol 9 (1456): 1456. Jul 2018. doi:10.3389/fimmu.2018.01456. PMID 30026741. 
  17. ↑ "The Mycobacterium tuberculosis prolyl dipeptidyl peptidase cleaves the N-terminal peptide of the immunoprotein CXCL-10". Biol Chem 404 (6): 633–43. Jan 2023. doi:10.1515/hsz-2022-0265. PMID 36632703. 

Further reading

  • "CD26/Dipeptidyl Peptidase IV in Lymphocyte Growth Regulation". Cellular Peptidases in Immune Functions and Diseases. Advances in Experimental Medicine and Biology. 421. 1997. pp. 127–40. doi:10.1007/978-1-4757-9613-1_17. ISBN 978-1-4757-9615-5. 
  • "The role of dipeptidyl peptidase IV (DP IV) enzymatic activity in T cell activation and autoimmunity". Biological Chemistry 383 (7–8): 1133–8. 2003. doi:10.1515/BC.2002.123. PMID 12437097. 
  • "CD26: a novel treatment target for T-cell lymphoid malignancies? (Review)". International Journal of Oncology 22 (3): 481–97. March 2003. doi:10.3892/ijo.22.3.481. PMID 12579300. 
  • "Dipeptidyl Peptidase IV Substrates". Dipeptidyl Aminopeptidases in Health and Disease. Advances in Experimental Medicine and Biology. 524. 2003. pp. 3–17. doi:10.1007/0-306-47920-6_1. ISBN 0-306-47717-3. 
  • "On the role of dipeptidyl peptidase IV in the digestion of an immunodominant epitope in celiac disease". Dipeptidyl Aminopeptidases in Health and Disease. Advances in Experimental Medicine and Biology. 524. 2003. pp. 181–7. doi:10.1007/0-306-47920-6_22. ISBN 0-306-47717-3. 
  • "CD26/dipeptidyl peptidase IV and its role in cancer". Histology and Histopathology 19 (4): 1345–51. October 2004. doi:10.14670/HH-19.1345. PMID 15375776. 

External links



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