TY - JOUR
T1 - A novel protein derived from the MUC1 gene by alternative splicing and frameshifting
AU - Levitin, Fiana
AU - Baruch, Amos
AU - Weiss, Mordechai
AU - Stiegman, Keren
AU - Hartmann, Mor Li
AU - Yoeli-Lerner, Merav
AU - Ziv, Ravit
AU - Zrihan-Licht, Sheila
AU - Shina, Sima
AU - Gat, Andrea
AU - Lifschitz, Beatrice
AU - Simha, Moshe
AU - Stadler, Yona
AU - Cholostoy, Alina
AU - Gil, Benny
AU - Greaves, David
AU - Keydar, Iafa
AU - Zaretsky, Joseph
AU - Smorodinsky, Nechama
AU - Wreschner, Daniel H.
PY - 2005/3/18
Y1 - 2005/3/18
N2 - Genes that have been designated the name "MUC" code for proteins comprising mucin domains. These proteins may be involved in barrier and protective functions. The first such gene to be characterized and sequenced is the MUC1 gene. Here we report a novel small protein derived from the MUC1 gene by alternative splicing that does not contain the hallmark of mucin proteins, the mucin domain. This protein termed MUC1/ZD retains the same N-terminal MUC1 sequences as all of the other known MUC1 protein isoforms. The common N-terminal sequences comprise the signal peptide and a subsequent stretch of 30 amino acids. In contrast, the MUC1/ZD C-terminal 43 amino acids are novel and result from a reading franteshifft engendered by a splicing event that forms MUC1/ZD. The expression of MUC1/ZD at the protein level in human tissues is demonstrated by Western blotting, immunohistochemistry, immunoprecipitation, and an ELISA. Utilization was made of affinity-purified MUC1/ZD-specific polyclonal antibodies as well as two different monoclonal antibodies that are monospecific for the MUC1/ZD protein. The MUC1/ZD protein is expressed in tissues as an oligomeric complex composed of monomers linked by disulfide bonds contributed by MUC1/ZD cysteine residues. MUC1/ZD protein expression did not parallel that of the tandem-repeat array-containing MUC1 protein. Results presented here demonstrate for the first time the expression of a novel MUC1 protein isoform MUC1/ZD, which is generated by an alternative splicing event that both deletes the tandem-repeat array and leads to a C-terminal reading frameshift.
AB - Genes that have been designated the name "MUC" code for proteins comprising mucin domains. These proteins may be involved in barrier and protective functions. The first such gene to be characterized and sequenced is the MUC1 gene. Here we report a novel small protein derived from the MUC1 gene by alternative splicing that does not contain the hallmark of mucin proteins, the mucin domain. This protein termed MUC1/ZD retains the same N-terminal MUC1 sequences as all of the other known MUC1 protein isoforms. The common N-terminal sequences comprise the signal peptide and a subsequent stretch of 30 amino acids. In contrast, the MUC1/ZD C-terminal 43 amino acids are novel and result from a reading franteshifft engendered by a splicing event that forms MUC1/ZD. The expression of MUC1/ZD at the protein level in human tissues is demonstrated by Western blotting, immunohistochemistry, immunoprecipitation, and an ELISA. Utilization was made of affinity-purified MUC1/ZD-specific polyclonal antibodies as well as two different monoclonal antibodies that are monospecific for the MUC1/ZD protein. The MUC1/ZD protein is expressed in tissues as an oligomeric complex composed of monomers linked by disulfide bonds contributed by MUC1/ZD cysteine residues. MUC1/ZD protein expression did not parallel that of the tandem-repeat array-containing MUC1 protein. Results presented here demonstrate for the first time the expression of a novel MUC1 protein isoform MUC1/ZD, which is generated by an alternative splicing event that both deletes the tandem-repeat array and leads to a C-terminal reading frameshift.
UR - http://www.scopus.com/inward/record.url?scp=20144381962&partnerID=8YFLogxK
U2 - 10.1074/jbc.M406943200
DO - 10.1074/jbc.M406943200
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AN - SCOPUS:20144381962
SN - 0021-9258
VL - 280
SP - 10655
EP - 10663
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 11
ER -