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Wolczynski, S.

Publications and source records attributed to Wolczynski, S..

2 recordsLinked to original sources

Chromosome-associated spot formation by human cytomegalovirus immediate early 1 (IE1) protein

HCMV is associated with severe disease in immunocompromised patients and is a cause of congenital disease. Already more than 30 years ago, IE1 was described to bind to mitotic chromosomes, however the implications of this finding have yet to be determined. HCMV can infect a wide range of cell types and was also detected in different tumours; however, the majority of molecular studies relating to this virus are performed in fibroblasts or monocytic cells. We examined the localization of HCMV IE1 across multiple cell types, including tumour cell lines, to better understand how the protein behaves in these cellular contexts. IE1 is one of the first HCMV genes expressed after lytic infection of the cell and it was observed to distribute evenly over the chromosomes in so-called "chromosome painting" pattern. In leukemia and glioblastoma cells we detected a novel mitotic localization pattern of IE1 - in chromosome-associated spots (CAS), in addition to "painting the chromosomes", as reported before. We demonstrate that the IE1 core domain mediates CAS localization and that the distribution pattern of IE1 on mitotic chromosomes is influenced by both the cell type being infected and the level of IE1 expression. The novel CAS localization of IE1 suggests a new, possibly cell-type specific function of this protein, distinct from its role in transcriptional regulation.

microbiology↗

Deletion of Letmd1 leads to the disruption of mitochondrial function in brown adipose tissue

Human cervical cancer oncogene (HCCR-1), also named as LETMD1, is a LETM-domain containing outer mitochondrial membrane protein which plays an important role in the carcinogenesis of cancers. Surprisingly, we found that loss of Letmd1 in mice leads to multiply severe abnormities, such as the brown adipose tissue (BAT) whitening, disruption of thermogenesis, cold-induced death, diet-induced obesity, hyperglycinemia and insulin resistance. Mechanistically, deletion of Letmd1 in BAT causes the reduction of mitochondrial calcium ion, which in turn results in the suppressed fission of mitochondria, and ultimately leads to the depletion of Ucp1-mediated BAT heat production. This study indicates that LETMD1 plays a crucial role in controlling BAT thermogenesis and energy homeostasis by regulating mitochondrial structures and functions, and also provides a novel insight for the clinical biomarker and therapeutical target of oncogene for the metabolic disorders. HighlightsO_LILetmd1 is an oncogene and also highly expressed in brown adipose tissue (BAT) of human and mice. C_LIO_LILoss of Letmd1 leads to BAT whitening, diet-induced obesity, hyperglycemia and insulin resistant. C_LIO_LILetmd1 knockout causes the disruption of thermogenesis and death at 4{degrees}C exposure. C_LIO_LIDeletion of Letmd1 results in mitochondrial calcium homeostasis disorders. C_LI Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=159 HEIGHT=200 SRC="FIGDIR/small/388199v2_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@bee6adorg.highwire.dtl.DTLVardef@11a7cc1org.highwire.dtl.DTLVardef@1f4699forg.highwire.dtl.DTLVardef@142699a_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗