S100 calcium-binding protein A2 (S100A2) is a protein that in humans is encoded by the S100A2gene[2] and it is located on chromosome 1q21 with other S100 proteins.
Tissue and subcellular distribution
S100A2, also known as CaN19 or S100L was first isolated from bovine lung tissue.[3] However, in human tissue it was discovered several years later, in the mammary epithelial cells.[4] Under normal circumstances it is highly expressed in human lungs, prostate, kidneys, hair follicles and salivary and mammary glands.[5] S100A2 is predominantly found in the nucleus, which is not very common in other S100 proteins. Moreover, it can also be found in the cytoplasm, and its distribution is rather diffuse. Its occurrence in cytoplasm is most likely dependent on calcium levels in the cell.[6][7][8] In the extracellular environment, it can be found as a homodimerin vivo and in vitro, but it also exists in monomeric, polymeric and multimeric forms. In multimeric form, it functions as a RAGE receptor ligand.[9]
Function
S100A2 is important in cytoskelet organization.[10] Also, S100A2 is induced by p53, which it interacts and participates in the transcription of p21.[11][12] It also plays a role in differentiation, regeneration of tissues and healing[13][14] and it was shown it attract eosinophils by chemotaxis.[15]
Clinical significance
Its expression is reduced in many types of cancer, thereby distinguishing the cancerous expression profile of the other proteins of the S100 group.[16][17][18] It has been reported that S100A2 is downregulated in lung, kidney, prostate cancer and melanoma.[16] Chromosomal rearrangements and altered expression of this gene have also been implicated in breast cancer.[19][20][7] In addition, its decline is associated with poor prognosis, disease progression, increased occurrence of metastasis and increased patient mortality.[21] Although in most cancers it has been found in reduced levels, there are studies that show that in some cases it is overproduced.[22][23]
References
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Wolf S, Haase-Kohn C, Pietzsch J (October 2011). "S100A2 in cancerogenesis: a friend or a foe?". Amino Acids. 41 (4): 849–61. doi:10.1007/s00726-010-0623-2. PMID20521072.
^Zhang T, Woods TL, Elder JT (November 2002). "Differential responses of S100A2 to oxidative stress and increased intracellular calcium in normal, immortalized, and malignant human keratinocytes". The Journal of Investigative Dermatology. 119 (5): 1196–201. doi:10.1046/j.1523-1747.2002.19520.x. PMID12445212.
^Deshpande R, Woods TL, Fu J, Zhang T, Stoll SW, Elder JT (September 2000). "Biochemical characterization of S100A2 in human keratinocytes: subcellular localization, dimerization, and oxidative cross-linking". The Journal of Investigative Dermatology. 115 (3): 477–85. doi:10.1046/j.1523-1747.2000.00078.x. PMID10951287.
^Brown GL, Nanney LB, Griffen J, Cramer AB, Yancey JM, Curtsinger LJ, et al. (July 1989). "Enhancement of wound healing by topical treatment with epidermal growth factor". The New England Journal of Medicine. 321 (2): 76–9. doi:10.1056/NEJM198907133210203. PMID2659995.
^Komada T, Araki R, Nakatani K, Yada I, Naka M, Tanaka T (March 1996). "Novel specific chemtactic receptor for S100L protein on guinea pig eosinophils". Biochemical and Biophysical Research Communications. 220 (3): 871–4. doi:10.1006/bbrc.1996.0496. PMID8607858.
^Gupta S, Hussain T, MacLennan GT, Fu P, Patel J, Mukhtar H (January 2003). "Differential expression of S100A2 and S100A4 during progression of human prostate adenocarcinoma". Journal of Clinical Oncology. 21 (1): 106–12. doi:10.1200/JCO.2003.03.024. PMID12506178.
^Suzuki F, Oridate N, Homma A, Nakamaru Y, Nagahashi T, Yagi K, et al. (December 2005). "S100A2 expression as a predictive marker for late cervical metastasis in stage I and II invasive squamous cell carcinoma of the oral cavity". Oncology Reports. 14 (6): 1493–8. doi:10.3892/or.14.6.1493. PMID16273244.
^Wang H, Zhang Z, Li R, Ang KK, Zhang H, Caraway NP, et al. (August 2005). "Overexpression of S100A2 protein as a prognostic marker for patients with stage I non small cell lung cancer". International Journal of Cancer. 116 (2): 285–90. doi:10.1002/ijc.21035. PMID15800916.
Schäfer BW, Heizmann CW (April 1996). "The S100 family of EF-hand calcium-binding proteins: functions and pathology". Trends in Biochemical Sciences. 21 (4): 134–40. doi:10.1016/S0968-0004(96)80167-8. PMID8701470.
Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J (December 1992). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis. 13 (12): 960–9. doi:10.1002/elps.11501301199. PMID1286667.
Schäfer BW, Wicki R, Engelkamp D, Mattei MG, Heizmann CW (February 1995). "Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family". Genomics. 25 (3): 638–43. doi:10.1016/0888-7543(95)80005-7. PMID7759097.
Gimona M, Lando Z, Dolginov Y, Vandekerckhove J, Kobayashi R, Sobieszek A, Helfman DM (March 1997). "Ca2+-dependent interaction of S100A2 with muscle and nonmuscle tropomyosins". Journal of Cell Science. 110 ( Pt 5) (5): 611–21. PMID9092943.
Böni R, Burg G, Doguoglu A, Ilg EC, Schäfer BW, Müller B, Heizmann CW (July 1997). "Immunohistochemical localization of the Ca2+ binding S100 proteins in normal human skin and melanocytic lesions". The British Journal of Dermatology. 137 (1): 39–43. doi:10.1111/j.1365-2133.1997.tb03698.x. PMID9274623.
Wicki R, Franz C, Scholl FA, Heizmann CW, Schäfer BW (October 1997). "Repression of the candidate tumor suppressor gene S100A2 in breast cancer is mediated by site-specific hypermethylation". Cell Calcium. 22 (4): 243–54. doi:10.1016/S0143-4160(97)90063-4. PMID9481475.
Mueller A, Bächi T, Höchli M, Schäfer BW, Heizmann CW (June 1999). "Subcellular distribution of S100 proteins in tumor cells and their relocation in response to calcium activation". Histochemistry and Cell Biology. 111 (6): 453–9. doi:10.1007/s004180050381. PMID10429967.
Hoyaux D, Decaestecker C, Heizmann CW, Vogl T, Schäfer BW, Salmon I, et al. (June 2000). "S100 proteins in Corpora amylacea from normal human brain". Brain Research. 867 (1–2): 280–8. doi:10.1016/S0006-8993(00)02393-3. PMID10837826.
Deshpande R, Woods TL, Fu J, Zhang T, Stoll SW, Elder JT (September 2000). "Biochemical characterization of S100A2 in human keratinocytes: subcellular localization, dimerization, and oxidative cross-linking". The Journal of Investigative Dermatology. 115 (3): 477–85. doi:10.1046/j.1523-1747.2000.00078.x. PMID10951287.
Nagy N, Hoyaux D, Gielen I, Schäfer BW, Pochet R, Heizmann CW, et al. (January 2002). "The Ca2+-binding S100A2 protein is differentially expressed in epithelial tissue of glandular or squamous origin". Histology and Histopathology. 17 (1): 123–30. doi:10.14670/HH-17.123. PMID11813862.
Kyriazanos ID, Tachibana M, Dhar DK, Shibakita M, Ono T, Kohno H, Nagasue N (2002). "Expression and prognostic significance of S100A2 protein in squamous cell carcinoma of the esophagus". Oncology Reports. 9 (3): 503–10. doi:10.3892/or.9.3.503. PMID11956617.
Zhang T, Woods TL, Elder JT (November 2002). "Differential responses of S100A2 to oxidative stress and increased intracellular calcium in normal, immortalized, and malignant human keratinocytes". The Journal of Investigative Dermatology. 119 (5): 1196–201. doi:10.1046/j.1523-1747.2002.19520.x. PMID12445212.
Hibi K, Fujitake S, Takase T, Kodera Y, Ito K, Akiyama S, et al. (September 2003). "Identification of S100A2 as a target of the DeltaNp63 oncogenic pathway". Clinical Cancer Research. 9 (11): 4282–5. PMID14519656.
