Cell：新的抗炎细胞信号通路被发现

生物谷

生物谷报道：来自UCLA的Jonsson 癌症中心的科学家们最近发现了一种全新的抗炎细胞信号通路，这或许是保持免疫反应精确平衡的重要机制。研究结果发表在6月份的《Cell》上，UCLA的血液学及肿瘤学教授，文章第一作者Ke Shuai认为，研究成果将带来新的治疗癌症和炎症反应疾病的方法。
Shuai表示："研究的重要成果在于发现了新的限制炎症和免疫的细胞路径。免疫系统对于对抗病原感染和杀死肿瘤细胞都很重要。这一发现能帮助我们设计新的调节免疫系统的药物。"
　　Shuai和同事发现了这种PIAS1抗炎路径，这是一种常被广泛的刺激物用来调解免疫系统并且触发炎症的路径。发炎是身体的一种对抗感染的自然防御，但是不平衡的炎症将使人们更易患上癌症等疾病。PIAS1路径帮助保持免疫系统的健康平衡。当遇到细菌和其它威胁时，重要的免疫调控基因将在细胞核中启动以对抗感染。Shuai和同事则发现，PIAS1能阻止免疫调控基因的产物，以防止产生过度炎症反应。在发生癌症时，免疫系统能被动员起来杀死癌细胞，这可以帮助研发抗癌疫苗。因此，一种能够减弱PIAS1路径的药物就可以用于增强免疫系统对抗癌症作用。除此之外，这类药物还可以对抗其它重要疾病，例如HIV等。
Shuai的研究小组下一步计划是研究利用小型化学分子来作用于PIAS1信号通路，从而达到治疗癌症和其它疾病的效果。

Figure 1. Identification of the PIAS1 Phosphorylation Site

(A) Top: BMMs were either untreated or treated with TNF (20 ng/ml) or LPS (10 ng/ml). Whole-cell extracts were subjected to western blot analyses using anti-PIAS1. Bottom: Same as the top panel except that whole-cell lysates from 293T cells untreated or treated with UV (100 J/m²) were analyzed. PIAS1^*, modified PIAS1.

(B) LC-tandem mass spectrometry analysis identifies UV-induced modification of PIAS1 to be serine 90 (S90) phosphorylation. Left: Plots of 717 m/z ion signal during the chromatographic elution reveal a species unique to the UV-treated sample (indicated by arrow). Right: MS/MS of this 2+ ion (716.84 m/z) displays productions indicative of phosphorylated VHSSPMPPTLpSPS. The site of phosphorylation is revealed by the 98 Da losses characteristic of phospho-ser/thr and by the phosphorylated y7 production.

(C) ³²P-labeling assays were performed with 293T cells expressing Flag-PIAS1(1–415) WT or the S90A mutant PIAS1. Whole-cell lysates were subjected to immunoprecipitation with anti-Flag, followed by autoradiography (top panel), or western blotting with anti-Flag (bottom panel).

(D) Same as in (C) except that the endogenous PIAS1 was ³²P-labeled and immunoprecipitation and western blotting were performed with anti-PIAS1.

原文出处：

Cell June 1, 2007: 129 (5)

Proinflammatory Stimuli Induce IKKα-Mediated Phosphorylation of PIAS1 to Restrict Inflammation and Immunityp903
Bin Liu, Yonghui Yang, Vasili Chernishof, Rachel R. Ogorzalek Loo, Hyunduk Jang, Samuel Tahk, Randy Yang, Sheldon Mink, David Shultz, Clifford J. Bellone, Joseph A. Loo, and Ke Shuai
[Summary] [Full Text] [PDF] [Supplemental Data]

相关基因：

PIAS1

Official Symbol PIAS1 and Name: protein inhibitor of activated STAT, 1 [Homo sapiens]
Other Aliases: DDXBP1, GBP, GU/RH-II, MGC141878, MGC141879, ZMIZ3
Other Designations: AR interacting protein; DEAD/H (Asp-Glu-Ala-Asp/His) box binding protein 1; protein inhibitor of activated STAT-1; protein inhibitor of activated STAT1; zinc finger, MIZ-type containing 3
Chromosome: 15; Location: 15q
Annotation: Chromosome 15, NC_000015.8 (66133625..66267466)
MIM: 603566
GeneID: 8554

作者简介：

Ke Shuai , Ph.D.

University of California, Los Angeles

Grants

Growth Inhibition of Breast Cancer Cells by Interferons		1995 (Cycle I)	$225,000
	Research Priority: Innovative Treatment > New drug design	1KB-0224
	Award Type: Career Development Awards > New Investigator

Periodicals

The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities
	Periodical: Journal of Biological Chemistry
	Author(s): Song, M.M., Shuai, K
	Yr: 1998	Vol: 273	Nbr:	Pgs: 35056-62
	Associated Grant: Growth Inhibition of Breast Cancer Cells by Interferons

The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities
	Periodical: Journal of Biological Chemistry
	Author(s): Song, M.M., Shuai, K
	Yr: 1998	Vol: 273	Nbr:	Pgs: 35056-62
	Associated Grant: Growth Inhibition of Breast Cancer Cells by Interferons