Probing the S100 protein family through genomic and functional analysis

Ravasi, Timothy; Hsu, Kang; Goyette, Jesse; Schroder, Kate; Yang, Zheng; Rahimi, Farid; Miranda, Les P.; Alewood, Paul F.; Hume, David; Geczy, Carolyn L.

doi:10.1016/j.ygeno.2004.02.002

Cited by 137 publications

(124 citation statements)

References 49 publications

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“…CD14 hi monocytes in both pig and human share with granulocytes the high expression of S100A8 (5). S100A8 has also been implicated in inflammation, and excessively high levels have been associated with recurrent infections (38,39).…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Monocyte Subsets in the Pig

Fairbairn

Kapétanovic

Beraldi

et al. 2013

The Journal of Immunology

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Human and mouse monocyte can be divided into two different subpopulations based on surface marker expression: CD14/16 and Ly6C/CX3CR1, respectively. Monocyte subpopulations in the pig were identified based on reciprocal expression of CD14 and the scavenger receptor CD163. The two populations, CD14hi-CD163low and CD14low-CD163hi, show approximately equal abundance in the steady-state. Culture of pig PBMCs in CSF1 indicates that the two populations are a maturation series controlled by this growth factor. Gene expression in pig monocyte subpopulations was profiled using the newly developed and annotated pig whole genome snowball microarray. Previous studies have suggested a functional equivalence between human and mouse subsets, but certain genes such as CD36, CLEC4E, or TREM-1 showed human-specific expression. The same genes were expressed selectively in pig monocyte subsets. However, the profiles suggest that the pig CD14low-CD163high cells are actually equivalent to intermediate human monocytes, and there is no CD14− CD16+ “nonclassical” population. The results are discussed in terms of the relevance of the pig as a model for understanding human monocyte function.

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Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Monocyte Subsets in the Pig

Fairbairn

Kapétanovic

Beraldi

et al. 2013

The Journal of Immunology

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“…S100B is a member of the S100 protein family of Ca 2ϩ -binding proteins initially named because of their solubility in 100% saturated ammonium sulfate (12). There are now over twenty S100 proteins widely distributed in human tissue (13)(14)(15), including a large numbers of cancers (16 -18), making it the largest family of EF-hand calcium-binding proteins (19). S100B, a 21.5-kDa symmetric homodimer, is overexpressed in malignant melanoma (18), anaplastic astrocytomas (20), and glio-blastomas (21), and in the case of malignant melanoma, high concentrations of S100B correlate directly with poor prognosis in patients (22).…”

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confidence: 99%

The Calcium-binding Protein S100B Down-regulates p53 and Apoptosis in Malignant Melanoma

Lin

Yang

Wilder

et al. 2010

Journal of Biological Chemistry

100

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The S100B-p53 protein complex was discovered in C8146A malignant melanoma, but the consequences of this interaction required further study. When S100B expression was inhibited in C8146As by siRNA (siRNA S100B ), wt p53 mRNA levels were unchanged, but p53 protein, phosphorylated p53, and p53 gene products (i.e. p21 and PIDD) were increased. siRNA S100B transfections also restored p53-dependent apoptosis in C8146As as judged by poly(ADP-ribose) polymerase cleavage, DNA ladder formation, caspase 3 and 8 activation, and aggregation of the Fas death receptor (؉UV); whereas, siRNA S100B had no effect in SK-MEL-28 cells containing elevated S100B and inactive p53 (p53R145L mutant). siRNA S100B -mediated apoptosis was independent of the mitochondria, because no changes were observed in mitochondrial membrane potential, cytochrome c release, caspase 9 activation, or ratios of pro-and anti-apoptotic proteins (BAX, Bcl-2, and Bcl-X L ). As expected, cells lacking S100B (LOX-IM VI) were not affected by siRNA S100B , and introduction of S100B reduced their UV-induced apoptosis activity by 7-fold, further demonstrating that S100B inhibits apoptosis activities in p53-containing cells. In other wild-type p53 cells (i.e. C8146A, UACC-2571, and UACC-62), S100B was found to contribute to cell survival after UV treatment, and for C8146As, the decrease in survival after siRNA S100B transfection (؉UV) could be reversed by the p53 inhibitor, pifithrin-␣. In summary, reducing S100B expression with siRNA was sufficient to activate p53, its transcriptional activation activities, and p53-dependent apoptosis pathway(s) in melanoma involving the Fas death receptor and perhaps PIDD. Thus, a well known marker for malignant melanoma, S100B, likely contributes to cancer progression by down-regulating the tumor suppressor protein, p53.In addition to regulating numerous genes and pathways involved in cell cycle control (1), the tumor suppressor protein, p53, is an important component for inducing apoptosis (2-4). The p53 protein activates the transcription of pro-apoptotic factors (BAX, Bak, Fas/APO-1, PIDD, etc.) as well as suppresses the transcription of anti-apoptotic genes (Bcl-2, Bcl-X L , etc.) (5, 6). In addition, p53 itself up-regulates apoptosis, without transcription activation, by directly localizing to mitochondria following DNA damage and interacting with anti-apoptotic proteins such as Bcl-X L to free pro-apoptotic proteins like BAX (2, 3, 5, 7). Under stress, the p53 protein can also contribute to apoptosis by facilitating the transport of death receptors such as Fas/APO-1 and/or Killer/DR5 from cytoplasmic stores to the cell surface as required for programmed cell death (5, 8). Although, it is now clear that p53-dependent pathways of apoptosis are numerous and are regulated in a cell-type and signalspecific manner (5).Apoptosis is initiated by a variety of stimuli, including withdrawal of growth factors, activation of specific receptors, such as Fas antigen and TNF receptor, and/or by exposure to UV radiation, ␥ irradiation, DNA-da...

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“…The S100A12 gene has been mapped to 1q21.2-1q22(1q21.3) and is located between the S100A8 and S100A9 genes (Ravasi et al, 2004). The S100A12 gene has a length of approximately 4.1 kbp and consists of three exons, which are divided by two introns of 900 and 400 bp.…”

Section: Gene and Protein Structurementioning

confidence: 99%