Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF) inhibits radiation-induced apoptosis in the leukemia cell line, CMK86 (O. Katoh et al., Cancer Res., 55: 5687-5692, 1995). To elucidate the molecular mechanisms underlying this inhibitory effect of VEGF, we attempted to identify a transcription factor involved in the cellular response to VEGF stimulation. We cloned the cDNA of a novel Kruppel-type zinc finger (ZNF) gene, ZK7, from a cDNA library constructed from the human leukemia cell line CMK86 after incubation with VEGF. This cDNA encoded a protein of 289 amino acids, which contained a Kruppel-associated box A-box domain at the NH2 terminus and seven ZNF motifs at the COOH terminus. These ZNF motifs were identical to those of HZF16 (M. Saleh et al., Am. J. Hum. Genet., 52: 192-203, 1993). ZK7 and HZF16 genes appear to be the splice variants transcribed from the same gene. Northern blotting and quantitative reverse transcription-PCR analysis revealed that expression of ZK7 mRNA in CMK86 cells and human hematopoietic progenitor cells was increased after VEGF stimulation, whereas that of HZF16 mRNA remained unchanged. To examine the function of ZK7 protein, we generated clones of a human monocytoid leukemia cell line, U937, which were stably transfected with ZK7 or HZF16 cDNA. Importantly, ZK7-overexpressing cells had lower sensitivity to ionizing radiation and the chemotherapeutic agent etoposide than U937 parent cells or HZF16-overexpressing cells. Therefore, ZK7 protein may be involved in the inhibitory effect of VEGF on apoptotic cell death in human hematopoietic cells.
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PMID:ZK7, a novel zinc finger gene, is induced by vascular endothelial growth factor and inhibits apoptotic death in hematopoietic cells. 1066 97

Hair cells in the auditory sensory organ are specialized mechanoreceptors common to mammalian and non-mammalian species. The mammalian cochlear outer hair cells (OHC) possess a distinct motile property, dubbed membrane-based electromotility, that enhances the receptor function. This electromotility is believed to be the basis of cochlear amplification that increases sensitivity of the mammalian ear to sound. Prestin, a unique voltage-sensitive motor molecule localized in the lateral membrane of OHC, is presumably responsible for OHC electromotility. It has been documented that prestin null-animals lack electromotility and suffer from approximately 50 dB loss of hearing sensitivity. To identify proteins that interact with prestin we carried out a yeast two-hybrid library screen using the C-terminal intracellular domain of prestin as bait. Seven bait-dependent prey clones were identified independently. Further analysis revealed that they encode partially over-lapping regions of a single protein: a transcriptional repressor, promyleocytic leukemia zinc finger protein (PLZF). PLZF encodes a POZ/domain Kruppel-type zinc finger transcription factor reported to have pro-apoptotic and anti-proliferative activity. The interaction between endogenous prestin and PLZF proteins in the cochlea was confirmed by co-immunoprecipitation using organ of Corti lysates. Furthermore, immunohistochemical studies strongly suggest that PLZF co-localizes with prestin near the lateral membrane of cochlear OHC. The physiological significance of this interaction remains to be explored.
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PMID:Promyelocytic leukemia zinc finger protein localizes to the cochlear outer hair cells and interacts with prestin, the outer hair cell motor protein. 1592 7