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1

PDZ domains - common players in the cell signaling.

100%

Jeleń F., Oleksy A., Śmietana K., Otlewski J.

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2003

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vol. 50

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issue 4

985-1017

EN

PDZ domains are ubiquitous protein interaction modules that play a key role in cellular signaling. Their binding specificity involves recognition of the carboxyl-terminus of various proteins, often belonging to receptor and ion channel families. PDZ domains also mediate more complicated molecular networks through PDZ-PDZ interactions, recognition of internal protein sequences or phosphatidylinositol moieties. The domains often form a tandem of multiple copies, but equally often such tandems or single PDZ domain occur in combination with other signaling domains (for example SH3, DH/PH, GUK, LIM, CaMK). Common occurrence of PDZ domains in Metazoans strongly suggests that their evolutionary appearance results from the complication of signaling mechanisms in multicellular organisms. Here, we focus on their structure, specificity and role in signaling pathways.

2

The toxic Doppelganger: on the ionic and molecular mimicry of cadmium

100%

Chmielowska-Bąk J., Izbiańska K., Deckert J.

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2013

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vol. 60

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issue 3

369-374

EN

Cadmium is a toxic heavy metal which can cause numerous alterations in cell functioning. Exposure to cadmium leads to generation of reactive oxygen species, disorders in membrane structure and functioning, inhibition of respiration, disturbances in ion homeostasis, perturbations in cell division, and initiation of apoptosis and necrosis. This heavy metal is considered a carcinogen by the Agency for Toxic Substances and Disease Registry. At least some of the described toxic effects could result from the ability of cadmium to mimic other divalent ions and alert signal transduction networks. This review describes the role of cadmium mimicry in its uptake, reactive oxygen species generation, alterations in calmodulin, Wnt/β-catenin and estrogen signaling pathways, and modulation of neurotransmission. The last section is dedicated to the single known case of a favorable function performed by cadmium mimicry: marine diatoms, which live in zinc deficient conditions, utilize cadmium as a cofactor in carbonic anhydrase - so far the only described cadmium enzyme.

3

Phosphatidic acid - a simple phospholipid with multiple faces

88%

Zegarlińska J., Piaścik M., Sikorski A., Czogalla A.

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2018

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vol. 65

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issue 2

163-171

EN

Phosphatidic acid (PA) is the simplest glycerophospholipid naturally occurring in living organisms, and even though its content among other cellular lipids is minor, it is drawing more and more attention due to its multiple biological functions. PA is a precursor for other phospholipids, acts as a lipid second messenger and, due to its structural properties, is also a modulator of membrane shape. Although much is known about interaction of PA with its effectors, the molecular mechanisms remain unresolved to a large degree. Throughout many of the well-characterized PA cellular sensors, no conserved binding domain can be recognized. Moreover, not much is known about the cellular dynamics of PA and how it is distributed among subcellular compartments. Remarkably, PA can play distinct roles within each of these compartments. For example, in the nucleus it behaves as a mitogen, influencing gene expression regulation, and in the Golgi membrane it plays a role in membrane trafficking. Here, we discuss how a biophysical experimental approach enabled PA behavior to be described in the context of a lipid bilayer and to what extent various physicochemical conditions may modulate the functional properties of this lipid. Understanding these aspects would help to unravel specific mechanisms of PA-driven membrane transformations and protein recruitment and thus would lead to a clearer picture of the biological role of PA.

4

TNFα-induced activation of NFκB protects against UV-induced apoptosis specifically in p53-proficient cells

88%

Szołtysek K., Pietranek K., Kalinowska-Herok M., Pietrowska M., Kimmel M., Widłak P.

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2008

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vol. 55

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issue 4

741-748

EN

The signaling pathways that depend on p53 or NFκB transcription factors are essential components of cellular responses to stress. In general, p53 is involved in either activation of cell cycle arrest or induction of apoptosis, while NFκB exerts mostly anti-apoptotic functions; both regulatory pathways apparently interfere with each other. Here we aimed to analyze the effects of NFκB activation on DNA damage-induced apoptosis, either p53-dependent or p53-independent, in a set of human cell lines. Four cell lines, HCT116 and RKO colon carcinoma, NCI-H1299 lung carcinoma and HL60 myeloblastoma, each of them in two congenic variants either containing or lacking transcriptionally competent p53, were used. Cells were incubated with TNFα cytokine to activate NFκB and then treated with ultraviolet or ionizing radiation to induce apoptosis, which was assessed by measurement of the sub-G1 cell fraction. We observed that treatment with TNFα resulted in a significant reduction in the frequency of apoptotic cells in UV-irradiated p53-proficient lines (with exception of the UV-resistant NCI-H1299 cells). This anti-apoptotic effect was lost when cells were pretreated with parthenolide, an inhibitor of NFκB activation. In marked contrast, TNFα-pretreatment of p53-deficient lines resulted in an increased frequency of apoptotic cells after UV irradiation (with exception of HL60 cells). Such anti- and pro-apoptotic influence of TNFα was less obvious in cells treated with ionizing radiation. The data clearly indicates functional interference of both signaling pathways upon the damage-induced apoptotic response, yet the observed effects are both cell type- and stimulus-specific.

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4 Acta Biochimica Polonica

1 2018

1 2013

1 2008

1 2003

1 Chmielowska-Bąk J.

1 Czogalla A.

1 Deckert J.

1 Izbiańska K.

1 Jeleń F.

1 Kalinowska-Herok M.

1 Kimmel M.

1 Oleksy A.

1 Otlewski J.

1 Piaścik M.

1 Pietranek K.

1 Pietrowska M.

1 Sikorski A.

1 Szołtysek K.

1 Widłak P.

1 Zegarlińska J.

1 Śmietana K.

PDZ domains - common players in the cell signaling.

The toxic Doppelganger: on the ionic and molecular mimicry of cadmium

Phosphatidic acid - a simple phospholipid with multiple faces

TNFα-induced activation of NFκB protects against UV-induced apoptosis specifically in p53-proficient cells