Heterodimer formation of the myeloid zinc finger 1 SCAN domain and association with promyelocytic leukemia nuclear bodies
LEUKEMIA RESEARCH
Authors: Noll, LeAnne; Peterson, Francis C.; Hayes, Paulette L.; Volkman, Brian F.; Sander, Tara
Abstract
Myeloid zinc finger 1 (MZF1) is a transcription factor that plays an important role in blood cell development. Previous reports indicate MZF1 is an essential factor whose abnormal expression results in cancer. However, the molecular mechanisms by which MZF1 functions in development and contributes to cancer progression remain unknown. MZF1 is a member of the SCAN domain family of zinc finger proteins (SCAN-ZFP) that form dimers via their highly conserved SCAN motif. To better understand the molecular mechanism of MZF1 function, we sought to characterize the cellular localization pattern of MZF1 in the context of SCAN dimerization. Here we provide evidence that MZF1 is a constituent of promyelocytic leukemia nuclear bodies (PML-NBs) and that the SCAN domain is necessary for association with these intranuclear structures. In addition, the SCAN-ZFP member ZNF24 was identified as a novel heterodimeric partner of MZF1 that also associates with PML-NBs in a unique ring-type pattern. Finally, we provide support that MZF1 protein may be modified by SUMOylation, which provides further support for localization of MZF1 protein complexes to PML-NBs. Altogether, these data suggest that MZF1 is recruited to PML-NBs and that the SCAN domain may play an integral role in regulating the localization of heterodimeric protein complexes to these intranuclear structures. (c) 2008 Elsevier Ltd. All rights reserved.
A Time-lapse, Label-free, Quantitative Phase Imaging Study of Dormant and Active Human Cancer Cells
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
Authors: Huang, Jing; Guo, Peng; Moses, Marsha A.
Abstract
The acquisition of the angiogenic phenotype is an essential component of the escape from tumor dormancy. Although several classic in vitro assays (e.g., proliferation, migration, and others) and in vivo models have been developed to investigate and characterize angiogenic and non-angiogenic cell phenotypes, these methods are time and labor intensive, and often require expensive reagents and instruments, as well as significant expertise. In a recent study, we used a novel quantitative phase imaging (QPI) technique to conduct time-lapse and labeling-free characterizations of angiogenic and non-angiogenic human osteosarcoma KHOS cells. A panel of cellular parameters, including cell morphology, proliferation, and motility, were quantitatively measured and analyzed using QPI. This novel and quantitative approach provides the opportunity to continuously and non-invasively study relevant cellular processes, behaviors, and characteristics of cancer cells and other cell types in a simple and integrated manner. This report describes our experimental protocol, including cell preparation, QPI acquisition, and data analysis.