Datasheet

生物学的記述

Specificity	14-3-3σ Antibody (Rabbit mAb) [E16M6] detects endogenous levels of total 14-3-3σ proteins.
Background	14-3-3 sigma (stratifin, encoded by SFN) is a unique member of the 14-3-3 family that is directly induced by the p53 tumor suppressor through a p53-responsive element located 1.8 kilobases upstream of its transcription start site, and this induction occurs in response to DNA-damaging agents including gamma irradiation. Introducing 14-3-3 sigma into cycling cells is sufficient on its own to produce a G2 arrest, and it achieves this by sequestering cyclin B and the kinase CDC2 in the cytoplasm, preventing the CDC2-cyclin B complex from entering the nucleus where it would otherwise trigger entry into mitosis; because the fission yeast 14-3-3 homologs rad24 and rad25 mediate a similar checkpoint function, this cytoplasmic sequestration mechanism for G2/M checkpoint control is conserved across eukaryotic evolution. Beyond this direct cytoplasmic retention of mitotic regulators, 14-3-3 sigma also engages in a positive feedback relationship with p53 itself: following DNA damage, 14-3-3 sigma physically interacts with p53 and stabilizes p53 protein levels by antagonizing the biological activity of Mdm2, specifically blocking Mdm2-mediated ubiquitination and nuclear export of p53, and separately facilitates p53 oligomerization, which enhances p53's transcriptional activity; because 14-3-3 sigma is itself a p53 target gene, this creates a feed-forward loop in which p53 induces 14-3-3 sigma, which in turn further stabilizes and activates p53. Consistent with this checkpoint role, overexpressing 14-3-3 sigma in a tetracycline-regulated system inhibits oncogene-driven tumorigenicity, directly demonstrating a tumor-suppressive function tied to this p53-stabilizing and G2/M-restraining activity. Across multiple epithelial cancer types, including breast, lung, prostate and skin cancers, the 14-3-3 sigma gene promoter is silenced by CpG methylation at an early stage of tumor development, disabling this p53-14-3-3 sigma feedback loop and the associated cytoplasmic sequestration of mitotic regulators, and this epigenetic loss is proposed to allow cells to evade senescence and to accumulate genomic instability during carcinogenesis.

Specificity

14-3-3σ Antibody (Rabbit mAb) [E16M6] detects endogenous levels of total 14-3-3σ proteins.

Background

14-3-3 sigma (stratifin, encoded by SFN) is a unique member of the 14-3-3 family that is directly induced by the p53 tumor suppressor through a p53-responsive element located 1.8 kilobases upstream of its transcription start site, and this induction occurs in response to DNA-damaging agents including gamma irradiation. Introducing 14-3-3 sigma into cycling cells is sufficient on its own to produce a G2 arrest, and it achieves this by sequestering cyclin B and the kinase CDC2 in the cytoplasm, preventing the CDC2-cyclin B complex from entering the nucleus where it would otherwise trigger entry into mitosis; because the fission yeast 14-3-3 homologs rad24 and rad25 mediate a similar checkpoint function, this cytoplasmic sequestration mechanism for G2/M checkpoint control is conserved across eukaryotic evolution. Beyond this direct cytoplasmic retention of mitotic regulators, 14-3-3 sigma also engages in a positive feedback relationship with p53 itself: following DNA damage, 14-3-3 sigma physically interacts with p53 and stabilizes p53 protein levels by antagonizing the biological activity of Mdm2, specifically blocking Mdm2-mediated ubiquitination and nuclear export of p53, and separately facilitates p53 oligomerization, which enhances p53's transcriptional activity; because 14-3-3 sigma is itself a p53 target gene, this creates a feed-forward loop in which p53 induces 14-3-3 sigma, which in turn further stabilizes and activates p53. Consistent with this checkpoint role, overexpressing 14-3-3 sigma in a tetracycline-regulated system inhibits oncogene-driven tumorigenicity, directly demonstrating a tumor-suppressive function tied to this p53-stabilizing and G2/M-restraining activity. Across multiple epithelial cancer types, including breast, lung, prostate and skin cancers, the 14-3-3 sigma gene promoter is silenced by CpG methylation at an early stage of tumor development, disabling this p53-14-3-3 sigma feedback loop and the associated cytoplasmic sequestration of mitotic regulators, and this epigenetic loss is proposed to allow cells to evade senescence and to accumulate genomic instability during carcinogenesis.

使用情報

Application

WB, IHC, IF

Dilution

WB	IHC	IF
1:1000	1:2000-1:10000	1:1000

Reactivity

Human, Mouse, Rat

Source

Rabbit Monoclonal Antibody

MW

28 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

プロトコール

References

https://pubmed.ncbi.nlm.nih.gov/14517281/
https://pubmed.ncbi.nlm.nih.gov/9659898/

Application Data

WB

Validated by Selleck

Lane 1: A431