Faculty Bibliography

A 10-year-old white boy presented clinically with thalassemia major facies, pallor, jaundice, and hepatomegaly. Investigation revealed the patient has hemoglobin (Hb) Lufkin concurrent with beta(0) thalassemia. DNA sequencing of the beta globin gene confirmed a GGC to a GAC mutation at codon 29 (gly to asp) for Hb Lufkin on the patient and also revealed a beta(0) thalassemia mutation, IVS-1-1 (G to A), on both the patient and his mother. Both parents lack the Hb Lufkin mutation. Molecular studies, human leukocyte antigen, and red blood cells phenotypic studies indicate spontaneous mutation of Hb Lufkin in this patient.

We identified a novel erythropoietin (Epo)-induced protein (CIP29) in lysates of human UT-7/Epo leukemia cells using two-dimensional gel analysis and cloned its full-length cDNA. CIP29 contains 210 amino acids with a predicted MW of 24 kDa, and has a N-terminal SAP DNA-binding motif. CIP29 expression was higher in cancer and fetal tissues than in normal adult tissues. CIP29 mRNA expression is cytokine regulated in hematopoietic cells, being up-regulated by Epo in UT7/Epo cells, and by thrombopoietin (Tpo), FLT3 ligand (FL) and stem cell factor (SCF) in primary human CD34(+) cells. Up-regulation of CIP29 in UT7/Epo cells by Epo was associated with cell cycle progression but not with antiapoptosis. Epo withdrawal reduced CIP29 expression concomitant with cell cycle arrest. Overexpression of CIP29-GFP in HEK293 cells enhances cell cycle progression. CIP29 appears to be a new cytokine regulated protein involved in normal and cancer cell proliferation.

BACKGROUND:The regulation of programmed cell death is critical to developmental homeostasis and normal morphogenesis of embryonic tissues. Survivin, a member of the inhibitors of apoptosis protein (IAP) family primarily expressed in embryonic cells, is both an anti-apoptosis and a pro-survival factor. Since our previous studies have demonstrated the importance of apoptosis during embryonic submandibular salivary gland (SMG) development, we postulated that survivin is a likely mediator of SMG epithelial cell survival. RESULTS:We investigated the developmental expression of survivin in Pseudoglandular (approximately E14), Canalicular (approximately E15) and Terminal Bud (approximately E17) Stage SMGs. We report a significant 26% increase in transcript levels between the Canalicular and Terminal Bud Stages. Immunohistochemical studies demonstrate nuclear-localized survivin protein in epithelial cells bounding forming lumina in Canalicular and Terminal Bud Stage SMGs. CONCLUSIONS:Survivin is known to be a pro-survival and anti-apoptotic factor. Given that survivin translocation into the nucleus is required for the induction of entry into the cell cycle and the inhibition of apoptosis, our demonstration of nuclear-localized survivin protein in presumptive ductal and proacinar lumen-bounding cells suggests that survivin may be a key mediator of embryonic SMG epithelial cell survival.