Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P04637 (
p53
)
77,613
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
p73, like its family member
p53
, can induce programmed cell death following DNA damage. Here, we report that this mechanism also involves endoplasmic reticulum (ER) stress and the transactivation of
scotin
, a protein identified recently as a p53 target able to induce ER stress. By using Tet-On inducible cell lines (Saos 2 osteosarcoma cells that lack
p53
), we observed that TAp73alpha elicits significant alterations in the morphology of the ER system, namely in the fine subcellular localization of calnexin. We found that both TAp73alpha and
p53
are strong inducers of
scotin
. On the other hand, the transcriptionally deficient short isoforms DeltaNp73alpha did not upregulate the steady-state mRNA level of
scotin
, as evaluated by real-time RT-PCR. Following the induction of
scotin
, ER staining with calnexin showed evidence of morphological alteration, with variations in the intracellular concentration of free calcium, visualized by fluo-3 staining. The induction of ER stress by p73 was further supported by the transcriptional induction of Gadd 153, a transcription factor induced under ER stress conditions. In conclusion, the data reported indicate the ability of TAp73alpha and
p53
(not DeltaNp73alpha) to elicit
scotin
transactivation and ER stress. This molecular mechanism might contribute to the effector events inducing apoptosis downstream of p73.
...
PMID:p73-alpha is capable of inducing scotin and ER stress. 1511 3
TP73, as a
TP53
homologue, drew the attention of tumor biologists because it is rarely mutated in human cancers and can induce cell cycle arrest and apoptosis by activating genes also regulated by
p53
. However, TP73 harbors an additional promoter that produces a dominant negative p73 protein (deltaNp73) having the opposite effect of the TAp73 protein. Thus, the regulation of
p53
responsive genes in the absence of
p53
relies on a critical balance between different p73 gene-derived proteins. Recent reports have described additional complexity in the mechanism of action of transcriptionally active p73 (TAp73) in the induction of cell death. The molecular mechanism through which p73 induces apoptosis involves (i) expression and changes in subcellular localization of
scotin
, producing an endoplasmic reticulum (ER) stress; and (ii) transactivation of PUMA and Bax, thus determining cell fate. On the contrary, deltaNp73 inhibits apoptosis, thus contributing to the oncogenic potential of neuroblastoma cells.
...
PMID:Mechanism of induction of apoptosis by p73 and its relevance to neuroblastoma biology. 1565 Feb 40
