May 2, 2008

Aliquots—Research highlights from VUMC laboratories

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Aliquots—Research highlights from VUMC laboratories

We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:

Arrested development

Within days of conception, a developing human embryo forms a small ball-like structure called a blastocyst that is uniquely able to “implant” in the mother’s uterus. Defects in the blastocyst prevent the embryo from implanting, a major cause of infertility.

Little is known about how the 16-cell morula embryo develops into a 32-cell blastocyst, a transition that Hehai Wang, Ph.D., B. C. Paria, Ph.D., and colleagues are exploring. The investigators focused on the protein ZO-1, part of the “tight junction” complexes that connect cells together and known to be expressed in the morula stage embryo. They introduced small interfering RNAs into 8-cell mouse embryos to “knock down” ZO-1 expression and followed embryo development in the laboratory. Embryos with little or no ZO-1 arrested at the morula stage.

The results, reported in Developmental Biology, reveal an important role for ZO-1 – and presumably tight junctions – in the process of morula to blastocyst development.

— Leigh MacMillan

Allergic to tumors

Mast cells, the immune cells known for their roles in allergic responses, mediate inflammation and a variety of physiological and pathological processes. Their presence in some cancers is associated with slower tumor progression, but their specific role in carcinogenesis is poorly understood.

In the April issue of Carcinogenesis, Mark Sinnamon, Ph.D., Lynn Matrisian, Ph.D., and colleagues show that intestinal tumors (adenomas) in a mouse model of intestinal cancer have increased numbers of mast cells and mast cell-associated enzymes. To further investigate the role of mast cells in intestinal tumors, they generated mice deficient in mast cells and crossed them with the cancer-prone mice. In the absence of mast cells, these mice had a significant increase in adenoma size and number. Isolated tumors had fewer apoptotic nuclei – markers of cell death – and fewer eosinophils, another allergy-related cell known to induce tumor cell death.

This study presents in vivo evidence for a protective role of mast cells in tumor development and has implications for development of anti-tumor therapies.

— Susanne Tranguch

‘Clp’ at the middle

Cytokinesis – the division of a cell’s cytoplasm – is initiated by the contractile ring, a band of proteins that constricts to split the dividing cell into two. A family of enzymes, called Cdc14 phosphatases, regulates several facets of the cell cycle, including cytokinesis.

Dawn Clifford, Ph.D., Kathy Gould, Ph.D., and colleagues have elucidated a role for one member of this family, called Clp1, during cytokinesis in fission yeast. They found that Clp1 directly binds to a protein responsible for assembly and localization of the contractile ring, called Mid1. This interaction “tethers” Clp1 to the contractile ring. The investigators generated yeast with a mutation in mid1 that disrupts this tethering, showing that aberrant Clp1 localization results in abnormal contractile ring stability and, ultimately, cytokinesis failure.

Their findings, reported in the April Journal of Cell Biology, outline the importance of Clp1’s interaction with Mid1 to ensuring the appropriate “divvying up” of the cell’s internal goods during cytokinesis.

— Susanne Tranguch

Missing link to ‘killin’ cancer

Of the genes that keep cell proliferation – and thus cancer – in check, the tumor suppressor p53 is the most frequently disrupted or lost in human cancers. Through intermediaries, or target genes, p53 can either halt cell division or prompt cancer cells to commit suicide, or apoptosis. But how a cell decides between death or arrested cell division is not fully understood.

Yong-jig Cho, Ph.D., and Peng Liang, Ph.D., screened for p53 target genes in lung cancer and colon cancer cell lines and discovered a novel gene – fittingly dubbed killin – that is necessary and sufficient for p53-induced apoptosis. Killin, they found, encodes a DNA-binding protein that inhibits DNA synthesis thereby halting DNA replication and triggering apoptosis.

The results, reported in the April 8 issue of the Proceedings of the National Academy of Sciences, suggest that killin is a “missing link” between p53 activation and the decision cells make that leads to cell death.

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012