Related Experiment Video

Updated: Mar 1, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.8K

Phosphorylation of p53 at threonine 155 is required for Jab1-mediated nuclear export of p53

Eun-Woo Lee1, Wonkyung Oh2, Hosung Paul Song3

  • 1Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.

BMB Reports
|May 26, 2017
PubMed

Insights

Jun activation-domain binding protein 1 (Jab1) triggers p53 nuclear export and degradation. Phosphorylation of p53 at threonine 155 is crucial for this Jab1-mediated process, impacting p53 regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Protein Biochemistry

Background:

  • Jun activation-domain binding protein 1 (Jab1) is known to induce p53 nuclear export and subsequent cytoplasmic degradation.
  • The precise molecular mechanisms governing Jab1-mediated p53 regulation remain incompletely elucidated.

Discussion:

  • Phosphorylation of p53 at threonine 155 (T155) is demonstrated as essential for Jab1-induced nuclear export.
  • Curcumin, an inhibitor of COP9 signalosome (CSN)-associated kinases, inhibits Jab1-stimulated p53 phosphorylation at T155.
  • The T155E mutant, mimicking phosphorylated p53, shows spontaneous cytoplasmic localization, preventable by leptomycin B (LMB).

Key Insights:

  • Substitution of T155 with valine (T155V) abrogates Jab1-mediated p53 nuclear export, confirming T155 phosphorylation's critical role.
  • The T155E mutant localizes to the cytoplasm independently of Mdm2, but its translocation is significantly enhanced by ectopic Hdm2 expression.
  • Jab1-mediated phosphorylation of p53 at Thr155 is the key event driving p53 nuclear export.

Outlook:

  • Further investigation into the interplay between Jab1, p53 phosphorylation at T155, and the ubiquitin-proteasome system.
  • Exploring the therapeutic potential of targeting Jab1-p53 interactions in cancer.
  • Elucidating the upstream kinases responsible for p53 T155 phosphorylation in response to Jab1.

More Related Videos

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

280
Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method09:32

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

Published on: September 10, 2017

11.5K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.8K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

2.1K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.4K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
5.1K