A novel protein derived from the MUC1 gene by alternative splicing and frameshifting
Fiana Levitin, Amos Baruch, Mordechai Weiss, Keren Stiegman, Mor Li Hartmann, Merav Yoeli-Lerner, Ravit Ziv, Sheila Zrihan-Licht, Sima Shina, Andrea Gat, Beatrice Lifschitz, Moshe Simha, Yona Stadler, Alina Cholostoy, Benny Gil, David Greaves, Iafa Keydar, Joseph Zaretsky, Nechama Smorodinsky, Daniel H. Wreschner*
HYBRIDOMA LABORATORY
The Shmunis School of Biomedicine and Cancer Research
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.
https://doi.org/10.1074/jbc.M406943200
10.1074/jbc.M406943200
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Alternative Splicing Medicine & Life Sciences 100%
Mucins Medicine & Life Sciences 33%
Tandem Repeat Sequences Medicine & Life Sciences 26%
Levitin, F., Baruch, A., Weiss, M., Stiegman, K., Hartmann, M. L., Yoeli-Lerner, M., Ziv, R., Zrihan-Licht, S., Shina, S., Gat, A., Lifschitz, B., Simha, M., Stadler, Y., Cholostoy, A., Gil, B., Greaves, D., Keydar, I., Zaretsky, J., Smorodinsky, N., & Wreschner, D. H. (2005). A novel protein derived from the MUC1 gene by alternative splicing and frameshifting. Journal of Biological Chemistry, 280(11), 10655-10663. https://doi.org/10.1074/jbc.M406943200
Levitin, Fiana ; Baruch, Amos ; Weiss, Mordechai et al. / A novel protein derived from the MUC1 gene by alternative splicing and frameshifting. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 11. pp. 10655-10663.
@article{f0738c87cdd442a389a21a7683805f4c,
title = "A novel protein derived from the MUC1 gene by alternative splicing and frameshifting",
abstract = "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.",
author = "Fiana Levitin and Amos Baruch and Mordechai Weiss and Keren Stiegman and Hartmann, {Mor Li} and Merav Yoeli-Lerner and Ravit Ziv and Sheila Zrihan-Licht and Sima Shina and Andrea Gat and Beatrice Lifschitz and Moshe Simha and Yona Stadler and Alina Cholostoy and Benny Gil and David Greaves and Iafa Keydar and Joseph Zaretsky and Nechama Smorodinsky and Wreschner, {Daniel H.}",
doi = "10.1074/jbc.M406943200",
journal = "Journal of Biological Chemistry",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
Levitin, F, Baruch, A, Weiss, M, Stiegman, K, Hartmann, ML, Yoeli-Lerner, M, Ziv, R, Zrihan-Licht, S, Shina, S, Gat, A, Lifschitz, B, Simha, M, Stadler, Y, Cholostoy, A, Gil, B, Greaves, D, Keydar, I, Zaretsky, J, Smorodinsky, N & Wreschner, DH 2005, 'A novel protein derived from the MUC1 gene by alternative splicing and frameshifting', Journal of Biological Chemistry, vol. 280, no. 11, pp. 10655-10663. https://doi.org/10.1074/jbc.M406943200
A novel protein derived from the MUC1 gene by alternative splicing and frameshifting. / Levitin, Fiana; Baruch, Amos; Weiss, Mordechai et al.
In: Journal of Biological Chemistry, Vol. 280, No. 11, 18.03.2005, p. 10655-10663.
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.
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.
U2 - 10.1074/jbc.M406943200
DO - 10.1074/jbc.M406943200
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
Levitin F, Baruch A, Weiss M, Stiegman K, Hartmann ML, Yoeli-Lerner M et al. A novel protein derived from the MUC1 gene by alternative splicing and frameshifting. Journal of Biological Chemistry. 2005 Mar 18;280(11):10655-10663. doi: 10.1074/jbc.M406943200