Regulation of a bifunctional mRNA results in synthesis of secreted and nuclear probasin.

Spence, Andrew M.; Sheppard, Patricia; Davie, James R.; Matuo, Yuhsi; Nishi, Nozomu; McKeehan, Wallace L.; Dodd, Janice G.; Matusik, Robert J.

doi:10.1073/pnas.86.20.7843

Cited by 81 publications

(47 citation statements)

References 32 publications

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“…Probasin mRNA expression, which is regulated by androgens, gives rise to both a secreted and a nuclear form of probasin [129], the relative abundance of the two forms being correlated with cell type. Probasin concentration also seems to be closely linked with cell age and state of differentiation, consistent with a role in cell regulation [128].…”

Section: Cell Regulationmentioning

confidence: 99%

The lipocalin protein family: structure and function

Flower¹

1996

Biochemical Journal

1,527

1,278

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The lipocalin protein family is a large group of small extracellular proteins. The family demonstrates great diversity at the sequence level ; however, most lipocalins share three characteristic conserved sequence motifs, the kernel lipocalins, while a group of more divergent family members, the outlier lipocalins, share only one. Belying this sequence dissimilarity, lipocalin crystal structures are highly conserved and comprise a single eight-stranded continuously hydrogen-bonded antiparallel β-barrel, which encloses an internal ligand-binding site. Together with two other families of ligand-binding proteins, the fatty-acid-binding proteins (FABPs) and the avidins, the lipocalins form part of an overall structural superfamily : the calycins. Members of the lipocalin family are characterized by several common molecular-

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Section: Cell Regulationmentioning

confidence: 99%

The lipocalin protein family: structure and function

Flower¹

1996

Biochemical Journal

1,527

1,278

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Section: Discussionmentioning

confidence: 99%

“…Examples include the transcription factors c-myc (39), Pit 1 (40), GATA-1 (41), and the prostate protein probasin (42). In the case of probasin, the use of alternative translation initiating sites accounts for the secreted and nuclear forms of the protein with the nuclear form lacking the N-terminal signal peptide (42). Interestingly, the amino acid sequence just following the first methionine of the ⌬LF mRNA contains a cluster of basic amino acids, which is similar to nuclear targeting signals (43,44).…”

Section: Discussionmentioning

confidence: 99%

Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines

Siebert

Huang

1997

Proc. Natl. Acad. Sci. U.S.A.

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Lactoferrin (LF), traditionally known as an iron-binding protein present in high concentrations in milk and various secretions, has emerged as a multifunctional protein involved in many aspects of the host defense against infection. Recently, LF has been shown to inhibit the growth of solid tumors and reduce experimental metastasis in mice, suggesting that LF also may play a role in the defense against tumorigenesis. Here we provide the sequence of the cDNA and promoter region, the chromosome assignment, and tissue expression pattern of a novel form of LF mRNA (⌬LF). The sequence of ⌬LF mRNA is nearly identical to that of LF mRNA; however, at the 5 end, we find a novel sequence that replaces the N-terminal signal peptide sequence of LF mRNA. We map the ⌬LF mRNA to human chromosome 3 and find that both ⌬LF and LF sequences colocalize to the same cloned 90-to 150-kb genomic DNA fragment. We further show that the ⌬LF mRNA is the product of alternative splicing of the LF gene and likely is specified by use of an alternative promoter. Although we find ⌬LF mRNA at various levels in 20 of 20 adult and fetal human tissues, we do not find ⌬LF mRNA in any of 14 diverse tumor-derived cell lines.

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“…Studies by Spence et al (29) and Bugler et al (30) have shown that proteins, such as prostatic probasin and basic fibroblast growth factor (bFGF), behave differently when proteins are located in the different organelles. Moreover, Feo et al (31) demonstrated that α-enolase, a glycolytic enzyme that catalyzes interconversion of 2-phosphoglycerate and phosphoenol-pyruvate in cytoplasm, could bind to the P2 promoter and function as a repressor for the transcription of c-myc oncogene.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Feo et al (31) demonstrated that α-enolase, a glycolytic enzyme that catalyzes interconversion of 2-phosphoglycerate and phosphoenol-pyruvate in cytoplasm, could bind to the P2 promoter and function as a repressor for the transcription of c-myc oncogene. Notably, nuclear prostatic probasin, bFGF and α-enolase are frequently truncated forms of the protein, which could expose the nuclear localization sequence (NLS) that is deeply embedded in the natural protein configuration (29,32), or these proteins could be translated from an alternate initiation site to affix an extra peptide containing a NLS motif to N-terminus of the cognate protein (30). Moreover, because part of the rTSß motif resembles enolase (28), it is therefore reasonable to suggest that rTSß behaves like enolase having dual functions depending upon where the protein is located.…”

Section: Discussionmentioning

confidence: 99%

Expression of rTSβ as a 5-fluorouracil resistance marker in patients with primary breast cancer

Kuo

Wang²,

Chow³

et al. 2008

Oncol Rep

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Abstract. Expression of thymidylate synthase (TS) in tumor cells is frequently suggested as an important prognostic factor for patients scheduled for chemotherapy with 5-fluorouracil (5-FU). However, clinical evidence does not fully support such an anticipation. We studied the expression of rTSß, a reverse orientation gene of TS, as a 5-FU resistance marker in patients with primary breast cancer. Expression of rTSß was examined in 129 patients with newly diagnosed breast cancer and five breast cancer cell lines by immunohistochemistry, immunocytochemistry and immunoblotting. Clinically, expression of rTSß was found to correlate with survival of the patients (p=0.023) when patients received chemotherapeutic regimen containing 5-FU. In vitro, rTSß expression was found to correlate with 5-FU resistance in breast cancer cell lines. Notably, in the 5-FU-resistant cells, rTSß was identified in the nucleus, whereas in the 5-FUsensitive cells, rTSß was found in the cytoplasm. Nuclear localization of rTSß was further found to be associated with protein farnesylation. Therefore, nuclear expression of rTSß could be a novel 5-FU resistance marker in patients with primary breast cancer. IntroductionBreast cancer is the second most prevalent malignancy and the fourth leading cause of cancer death in Taiwanese women (1). Although the death rate of uterine cervical cancer has decreased significantly in the past two decades due to the improvement in the early detection of the disease by pap smear among women over 35 years of age; for breast cancer, not only has the incidence increased markedly, but also the age of tumor occurrence has decreased dramatically, which is about ten years younger than that of the Western population (2-4).Clinically, depending upon the status of estrogen and/or progesterone receptors in cancer cells, some patients receive non-steroidal anti-estrogen tamoxifen for hormonal therapy (5). However, most of the patients could only choose adjuvant chemotherapy containing 5-fluorouracil (5-FU) after surgery. 5-FU is a pro-drug that is converted to fluorouridine to interfere with RNA synthesis, or to 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) to inhibit thymidylate synthase (TS) and the consequent DNA synthesis. In the presence of N 5 , 10 -methylene tetrahydrofolate, FdUMP further forms a stable ternary complex with TS to inhibit synthesis of deoxythymidine monophosphate (dTMP) (reviewed in ref. 6). TS expression in tumor cells is considered as a key prognostic factor for patients receiving chemotherapy containing 5-FU (7).However, clinical evidence did not fully support this expectation (6,(8)(9)(10)(11)(12)(13). On the other hand, expression of the rTS (ENOSF1) gene (14-16) was found to be closely associated with 5-FU sensitivity besides nucleotide metabolism-related enzymes, e.g., thymidine phosphorylase, ribonucleotide reductase, uridine phosphorylase and thymidine kinase (17-19) that directly affects pyrimidine synthesis in de novo or salvage pathways (11).The rTS is located with the TS gene on the...

show abstract

Regulation of a bifunctional mRNA results in synthesis of secreted and nuclear probasin.

Cited by 81 publications

References 32 publications

The lipocalin protein family: structure and function

The lipocalin protein family: structure and function

Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines

Expression of rTSβ as a 5-fluorouracil resistance marker in patients with primary breast cancer

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