Maspin

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Serpin peptidase inhibitor, clade B (ovalbumin), member 5

PDB rendering based on 1wz9.
Available structures
PDBOrtholog search: PDBe, RCSB
Identifiers
SymbolsSERPINB5; PI5; maspin
External IDsOMIM154790 MGI109579 HomoloGene20580 GeneCards: SERPINB5 Gene
RNA expression pattern
PBB GE SERPINB5 204855 at tn.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez526820724
EnsemblENSG00000206075ENSMUSG00000067006
UniProtP36952P70124
RefSeq (mRNA)NM_002639NM_009257
RefSeq (protein)NP_002630NP_033283
Location (UCSC)Chr 18:
61.14 – 61.17 Mb
Chr 1:
106.86 – 106.88 Mb
PubMed search[1][2]
 
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Serpin peptidase inhibitor, clade B (ovalbumin), member 5

PDB rendering based on 1wz9.
Available structures
PDBOrtholog search: PDBe, RCSB
Identifiers
SymbolsSERPINB5; PI5; maspin
External IDsOMIM154790 MGI109579 HomoloGene20580 GeneCards: SERPINB5 Gene
RNA expression pattern
PBB GE SERPINB5 204855 at tn.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez526820724
EnsemblENSG00000206075ENSMUSG00000067006
UniProtP36952P70124
RefSeq (mRNA)NM_002639NM_009257
RefSeq (protein)NP_002630NP_033283
Location (UCSC)Chr 18:
61.14 – 61.17 Mb
Chr 1:
106.86 – 106.88 Mb
PubMed search[1][2]

Maspin (mammary serine protease inhibitor) also known as serpin B5 is a protein that in humans is encoded by the SERPINB5 gene.[1] This protein belongs to the serpin (serine protease inhibitor) superfamily.[1] SERPINB5 also functions as a tumor suppressor gene in epithelial cells. The expressed protein suppresses the ability of cancer cells to invade and metastasize other tissues. The protein also functions as an angiogenesis inhibitor.[2]

Tissue distribution[edit]

Maspin is expressed in the prostate, testis, intestine, tongue, lung, and the thymus.[1]

Serpin superfamily[edit]

Maspin is a member of the serpin superfamily of serine protease inhibitors.[1] The primary function of most members of this family is to regulate the breakdown of proteins by inhibiting the catalytic activity of proteinases. Through this mechanism of action, serpins regulate a number of cellular processes including phagocytosis, coagulation, and fibrinolysis.[3]

Serpins have a complex structure, a key component of which is the reactive site loop, RSL.[4] Inhibitory serpins transition between a stress and relaxed stage. The catalytic serine residue in the protease target attacks the stressed conformation of the RSL loop to form an acyl intermediate. The loop then undergoes a conformational change to the relaxed state irreversibly trapping the protease in an inactive state. Hence the serpine functions as a suicide inhibitor of the protease.[5] This transition does not occur in serpins that lack inhibitory activity.[4]

Function[edit]

Though maspin is a part of the serpin superfamily, its mechanism of action differs somewhat from other members of the family. More specifically, the RSL loop in maspin does not transition between a stressed and relaxed state and is shorter than the RSL loop in other serpins. However this shorter loop is necessary for maspin’s ability to suppress tumors by inhibiting cell invasion and motility. Furthermore, while maspin is an inhibitory serpin, but does not inhibit serine proteinases.[4] Instead, maspin functions as an inhibitor of histone deacetylase 1 (HDAC1).[6]

Tumors require blood in order to proliferate. Tumors invade other cells and begin to spread through a process known as metastasis. Metastasis is one of the key steps in cancer progression that causes cancer-related deaths. Maspin has been shown to inhibit all of these functions.[7] Maspin was able to inhibit the invasion of breast cancer. Normal mRNA expresses maspin, but tumor-derived mammary epithelial cells do not.[4] The consistent down regulation of maspin in breast cancer suggests maspin place a role in tumor suppression.[7] Maspin significantly correlates with tumor differentiation grade or lymph node status, but not with recurrence rates.[8] Maspin reduced the motility of tumor cells by 75 percent within 24 hours.[4]

Maspin treatment of breast cancer cells leads to increased focal adhesions and stress fibers that in turn reduce cell motility.[9] Less motile breast cancer cells were able to “revert to a more epithelial-like phenotype”.[9] When tumor cells are treated with maspin, 53 percent of the tumors stopped growing completely with in a week.[10] Tumor growth returned once the addition of maspin ceased. In addition, maspin able to regulate motility.[9]

Clinical significance[edit]

Deficiency in the expression of maspin been associated with increased risks of prostate and breast cancer.[11]

It has also been associated with tumors of the pancreas.[12]

References[edit]

  1. ^ a b c d Khalkhali-Ellis Z (December 2006). "Maspin: the new frontier". Clin. Cancer Res. 12 (24): 7279–83. doi:10.1158/1078-0432.CCR-06-1589. PMC 3175762. PMID 17189399. 
  2. ^ Sager R, Sheng S, Pemberton P, Hendrix MJ (1997). "Maspin. A tumor suppressing serpin". Adv. Exp. Med. Biol. 425: 77–88. PMID 9433491. 
  3. ^ Potempa J, Korzus E, Travis J (June 1994). "The serpin superfamily of proteinase inhibitors: structure, function, and regulation". J. Biol. Chem. 269 (23): 15957–60. PMID 8206889. 
  4. ^ a b c d e Sager R, Sheng S, Pemberton P, Hendrix MJ (1996). "Maspin: a tumor suppressing serpin". Curr. Top. Microbiol. Immunol. 213 (1): 51–64. PMID 8814994. 
  5. ^ Bailey CM, Khalkhali-Ellis Z, Seftor EA, Hendrix MJ (December 2006). "Biological functions of maspin". J. Cell. Physiol. 209 (3): 617–24. doi:10.1002/jcp.20782. PMID 17001697. 
  6. ^ Lonardo F, Li X, Kaplun A, Soubani A, Sethi S, Gadgeel S, Sheng S (June 2010). "The natural tumor suppressor protein maspin and potential application in non small cell lung cancer". Curr. Pharm. Des. 16 (16): 1877–81. doi:10.2174/138161210791208974. PMC 2908495. PMID 20337574. 
  7. ^ a b Sheng S, Pemberton PA, Sager R (December 1994). "Production, purification, and characterization of recombinant maspin proteins". J. Biol. Chem. 269 (49): 30988–93. PMID 7983035. 
  8. ^ Marioni G, Staffieri C, Staffieri A, De Filippis C, Blandamura S (May 2009). "MASPIN tumour-suppressing activity in head and neck squamous cell carcinoma: emerging evidence and therapeutic perspectives". Acta Otolaryngol. 129 (5): 476–80. doi:10.1080/00016480802256079. PMID 18615330. 
  9. ^ a b c Odero-Marah VA, Khalkhali-Ellis Z, Chunthapong J, Amir S, Seftor RE, Seftor EA, Hendrix MJ (2003). "Maspin regulates different signaling pathways for motility and adhesion in aggressive breast cancer cells". Cancer Biol. Ther. 2 (4): 398–403. PMID 14508113. 
  10. ^ Zhang M, Volpert O, Shi YH, Bouck N (February 2000). "Maspin is an angiogenesis inhibitor". Nat. Med. 6 (2): 196–9. doi:10.1038/72303. PMID 10655109. 
  11. ^ Shao LJ, Shi HY, Ayala G, Rowley D, Zhang M (July 2008). "Haploinsufficiency of the maspin tumor suppressor gene leads to hyperplastic lesions in prostate". Cancer Res. 68 (13): 5143–51. doi:10.1158/0008-5472.CAN-08-0163. PMC 2518316. PMID 18593913. 
  12. ^ Kashima K, Ohike N, Mukai S, Sato M, Takahashi M, Morohoshi T (February 2008). "Expression of the tumor suppressor gene maspin and its significance in intraductal papillary mucinous neoplasms of the pancreas". HBPD INT 7 (1): 86–90. PMID 18234645. 

Further reading[edit]

External links[edit]