[杏林风采]协和与基因组所的Nature Genetics [复制链接]

协和肿瘤研究所林东昕与中科院基因组所曾长青。
http://www.nature.com/ng/journal/v39/n5/full/ng2030.html#a1

Nature Genetics 39, 605 - 613 (2007)
Published online: 22 April 2007 | doi:10.1038/ng2030

A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers

Tong Sun1,4, Yang Gao2,4, Wen Tan1, Sufang Ma2, Yuankai Shi3, Jiarui Yao3, Yongli Guo1, Ming Yang1, Xuemei Zhang1, Qingrun Zhang2, Changqing Zeng2 & Dongxin Lin1


  1. Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  2. Beijing Genomics Institute, Chinese Academy of Sciences, Beijing, China.
  3. Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  4. These authors contributed equally to this work.

Correspondence to: Dongxin Lin1 e-mail: dlin@public.bta.net.cn

Correspondence to: Changqing Zeng2 e-mail: czeng@genomics.org.cn

Abstract

Caspases are important in the life and death of immune cells and therefore influence immune surveillance of malignancies. We tested whether genetic variants in CASP8, CASP10 and CFLAR, three genes important for death receptor–induced cell killing residing in tandem order on chromosome 2q33, are associated with cancer susceptibility. Using a haplotype-tagging SNP approach, we identified a six-nucleotide deletion (-652 6N del) variant in the CASP8 promoter associated with decreased risk of lung cancer. The deletion destroys a stimulatory protein 1 binding site and decreases CASP8 transcription. Biochemical analyses showed that T lymphocytes with the deletion variant had lower caspase-8 activity and activation-induced cell death upon stimulation with cancer cell antigens. Case-control analyses of 4,995 individuals with cancer and 4,972 controls in a Chinese population showed that this genetic variant is associated with reduced susceptibility to multiple cancers, including lung, esophageal, gastric, colorectal, cervical and breast cancers, acting in an allele dose–dependent manner. These results support the hypothesis that genetic variants influencing immune status modify cancer susceptibility.

Nature Genetics,05年IF25.797，强啊！

NIBS的马力耕和邵峰今年各发了一篇SCIENCE, 30分，更高一些。
ION今年有篇cell，本版前面贴过。
1: Science. 2007 Mar 23;315(5819):1712-6. Epub 2007 Mar 8.


A G protein-coupled receptor is a plasma membrane receptor for the plant hormone
abscisic acid.

Liu X, Yue Y, Li B, Nie Y, Li W, Wu WH, Ma L.

National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun
Life Science Park, Beijing 102206, China.

The plant hormone abscisic acid (ABA) regulates many physiological and
developmental processes in plants. The mechanism of ABA perception at the cell
surface is not understood. Here, we report that a G protein-coupled receptor
genetically and physically interacts with the G protein alpha subunit GPA1 to
mediate all known ABA responses in Arabidopsis. Overexpressing this receptor
results in an ABA-hypersensitive phenotype. This receptor binds ABA with high
affinity at physiological concentration with expected kinetics and
stereospecificity. The binding of ABA to the receptor leads to the dissociation
of the receptor-GPA1 complex in yeast. Our results demonstrate that this G
protein-coupled receptor is a plasma membrane ABA receptor.



2: Science. 2007 Feb 16;315(5814):1000-3.

The phosphothreonine lyase activity of a bacterial type III effector family.

Li H, Xu H, Zhou Y, Zhang J, Long C, Li S, Chen S, Zhou JM, Shao F.

National Institute of Biological Sciences, Beijing, 102206, China.

Pathogenic bacteria use the type III secretion system to deliver effector
proteins into host cells to modulate the host signaling pathways. In this study,
the Shigella type III effector OspF was shown to inactivate mitogen-activated
protein kinases (MAPKs) [extracellular signal-regulated kinases 1 and 2
(Erk1/2), c-Jun N-terminal kinase, and p38]. OspF irreversibly removed phosphate
groups from the phosphothreonine but not from the phosphotyrosine residue in the
activation loop of MAPKs. Mass spectrometry revealed a mass loss of 98 daltons
in p-Erk2, due to the abstraction of the alpha proton concomitant with cleavage
of the C-OP bond in the phosphothreonine residue. This unexpected enzymatic
activity, termed phosphothreonine lyase, appeared specific for MAPKs and was
shared by other OspF family members.