Sho1p connects the plasma membrane with proteins of the cytokinesis network through multiple isomeric interaction states.

An understanding of cytokinesis at the molecular level requires a detailed description of the protein complexes that perform central activities during this process. The proteins Hof1p, Cyk3p, Inn1p and Myo1p each represent one of the four genetically defined and partially complementary pathways of cytokinesis in the yeast Saccharomyces cerevisiae. Here we show that the osmosensor Sho1p is required for correct cell-cell separation. Shortly before cytokinesis Sho1p sequentially assembles with Hof1p, Inn1p and Cyk3p, into a complex (the HICS complex) that might help to connect the membrane with the actin-myosin ring. The HICS complex is formed exclusively through interactions between three SH3 domains located in Cyk3p, Hof1p and Sho1p, and five acceptor sites found in Cyk3p, Hof1p and Inn1p. Owing to the overlapping binding specificities of its members the HICS complex is best described as ensembles of isomeric interaction states that precisely coordinate the different functions of the interactors during cytokinesis.

[Mitochondria and cell death]. / Mitochondrium a smierc komórki.

In living cells, apoptosis is effected through many different pathways. Programmed cell death (PCD) may proceed with the involvement of membrane receptors, mitochondria, granzyme B, or the endoplasmic reticulum. The mitochondrial pathway is initiated from within the cell as a consequence of changes in reductive potential. It may also be caused by DNA mutation or various disturbances in the cell's metabolism. In some cases, the intrinsic pathway is connected with the extrinsic one, generated by the cell's environment. The central organelle which initiates the intrinsic pathway is the mitochondrion. Changes in the permeability of the mitochondrial outer membrane cause an outflow of cytochrom c, which interacts with cytoplasmic factor Apaf-1 and procaspase 9, in the presence of ATP, and thus triggers the caspase cascade. Apart from cytochrom c, more than 40 regular or executor particles involved in apoptosis might be released from the mitochondrion. These include Smac/DIABLO, Omi/HTR A2, endonuclease G, AIF, and IAP. Moreover, regulatory functions are performed by Bcl-2 family proteins present in the cytoplasm that affect mitochondrial membrane permeability and by heat shock proteins (HSPs), both of these regulating caspase function. The phenomenon of programmed cell death is the main subject of research for many groups of scientists. There are still many aspects which need to be elucidated.

Apaf-1 expression in human cutaneous melanoma progression and in pigmented nevi.

Malignant melanoma is notoriously refractive to therapy and resistant to apoptosis. This may reflect the downregulation of Apaf-1, an important mediator of mitochondrial-dependent apoptosis, observed in vitro in melanoma cell lines and by immunohistochemistry for Apaf-1 protein in histological samples of primary and metastatic melanomas. Although it has been suggested that loss of Apaf-1 expression may be an indicator of malignant transformation in melanoma, previous studies on Apaf-1 expression in benign pigmented nevi were performed without reference to their histologic type. Here we have evaluated the expression of Apaf-1 mRNA by fluorescence in situ hybridization and of Apaf-1 protein by immunohistochemistry in a large panel of human melanomas and in eight types of pigmented nevi, considered potential precursors for cutaneous melanoma. We observe a strong negative correlation between melanoma progression assessed according to Clark classification and the expression of Apaf-1. A significant decrease in Apaf-1 expression was observed between Clark II and Clark III lesions, the stages usually associated with a transition from horizontal to vertical growth phase of melanoma. There was also statistically significant difference in Apaf-1 mRNA expression between melanomas of Breslow thickness <1 mm and >4 mm. No Apaf-1 expression could be detected in lymph node melanoma metastases. These results suggest that Apaf-1 expression may become a prognostic marker for progress of human cutaneous melanoma and further support the notion that loss of Apaf-1 may be an important contributory factor in the development of the disease.