Abstract
doc-1 is a putative tumor suppressor gene isolated and identified from the hamster oral cancer model. Here, we report the molecular cloning and the functional characterization of the human ortholog of the hamster doc-1 gene. Human doc-1 cDNA is 1.6 kilobase pairs in length and encodes for a 115-amino acid polypeptide (12.4 kDa, pI 9.53). Sequence analysis showed 98% identity between human and hamster doc-1 protein sequences. DOC-1 is expressed in all normal human tissues examined. In oral keratinocytes, expression of DOC-1 is restricted to normal oral keratinocytes. By immunostaining of normal human mucosa, DOC-1 is detected in both the cytoplasm and nuclei of basal oral keratinocytes; while in suprabasilar cells, it is primarily found in the nuclei. Human oral cancers in vivo did not exhibit immunostaining for DOC-1. Like murine DOC-1, human DOC-1 associates with DNA polymerase α/primase and mediates the phosphorylation of the large p180 catalytic subunit, suggesting it may be a potential regulator of DNA replication in the S phase of the cell cycle. Using a human doc-1 cosmid as a probe, human doc-1 is mapped to chromosome 12q24. We identified four exons in the entire human doc-1 gene and determined the intron-exon boundaries. By polymerase chain reaction and direct sequencing, we examined premalignant oral lesion and oral cancer cell lines and found no intragenic mutations.
| Original language | English |
|---|---|
| Pages (from-to) | 6704-6709 |
| Number of pages | 6 |
| Journal | Journal of Biological Chemistry |
| Volume | 273 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Mar 20 1998 |
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ASJC Scopus subject areas
- Biochemistry
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Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene doc-1. / Tsuji, Takanori; Duh, Fuh Mei; Latif, Farida; Popescu, Nicolas C.; Zimonjic, Drazen B.; McBride, Jim; Matsuo, Kou; Ohyama, Hiroe; Todd, Randy; Nagata, Emi; Terakado, Nagaaki; Sasaki, Akira; Matsumura, Tomohiro; Lerman, Michael I.; Wong, David T W.
In: Journal of Biological Chemistry, Vol. 273, No. 12, 20.03.1998, p. 6704-6709.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene doc-1
AU - Tsuji, Takanori
AU - Duh, Fuh Mei
AU - Latif, Farida
AU - Popescu, Nicolas C.
AU - Zimonjic, Drazen B.
AU - McBride, Jim
AU - Matsuo, Kou
AU - Ohyama, Hiroe
AU - Todd, Randy
AU - Nagata, Emi
AU - Terakado, Nagaaki
AU - Sasaki, Akira
AU - Matsumura, Tomohiro
AU - Lerman, Michael I.
AU - Wong, David T W
PY - 1998/3/20
Y1 - 1998/3/20
N2 - doc-1 is a putative tumor suppressor gene isolated and identified from the hamster oral cancer model. Here, we report the molecular cloning and the functional characterization of the human ortholog of the hamster doc-1 gene. Human doc-1 cDNA is 1.6 kilobase pairs in length and encodes for a 115-amino acid polypeptide (12.4 kDa, pI 9.53). Sequence analysis showed 98% identity between human and hamster doc-1 protein sequences. DOC-1 is expressed in all normal human tissues examined. In oral keratinocytes, expression of DOC-1 is restricted to normal oral keratinocytes. By immunostaining of normal human mucosa, DOC-1 is detected in both the cytoplasm and nuclei of basal oral keratinocytes; while in suprabasilar cells, it is primarily found in the nuclei. Human oral cancers in vivo did not exhibit immunostaining for DOC-1. Like murine DOC-1, human DOC-1 associates with DNA polymerase α/primase and mediates the phosphorylation of the large p180 catalytic subunit, suggesting it may be a potential regulator of DNA replication in the S phase of the cell cycle. Using a human doc-1 cosmid as a probe, human doc-1 is mapped to chromosome 12q24. We identified four exons in the entire human doc-1 gene and determined the intron-exon boundaries. By polymerase chain reaction and direct sequencing, we examined premalignant oral lesion and oral cancer cell lines and found no intragenic mutations.
AB - doc-1 is a putative tumor suppressor gene isolated and identified from the hamster oral cancer model. Here, we report the molecular cloning and the functional characterization of the human ortholog of the hamster doc-1 gene. Human doc-1 cDNA is 1.6 kilobase pairs in length and encodes for a 115-amino acid polypeptide (12.4 kDa, pI 9.53). Sequence analysis showed 98% identity between human and hamster doc-1 protein sequences. DOC-1 is expressed in all normal human tissues examined. In oral keratinocytes, expression of DOC-1 is restricted to normal oral keratinocytes. By immunostaining of normal human mucosa, DOC-1 is detected in both the cytoplasm and nuclei of basal oral keratinocytes; while in suprabasilar cells, it is primarily found in the nuclei. Human oral cancers in vivo did not exhibit immunostaining for DOC-1. Like murine DOC-1, human DOC-1 associates with DNA polymerase α/primase and mediates the phosphorylation of the large p180 catalytic subunit, suggesting it may be a potential regulator of DNA replication in the S phase of the cell cycle. Using a human doc-1 cosmid as a probe, human doc-1 is mapped to chromosome 12q24. We identified four exons in the entire human doc-1 gene and determined the intron-exon boundaries. By polymerase chain reaction and direct sequencing, we examined premalignant oral lesion and oral cancer cell lines and found no intragenic mutations.
UR - http://www.scopus.com/inward/record.url?scp=15544391299&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=15544391299&partnerID=8YFLogxK
U2 - 10.1074/jbc.273.12.6704
DO - 10.1074/jbc.273.12.6704
M3 - Article
C2 - 9506968
AN - SCOPUS:15544391299
VL - 273
SP - 6704
EP - 6709
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 12
ER -