Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters

Database
Language
Affiliation country
Publication year range
1.
FEBS Lett ; 598(12): 1453-1464, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38811347

ABSTRACT

Microtubules are a major component of the cytoskeleton and can accumulate a plethora of modifications. The microtubule detyrosination cycle is one of these modifications; it involves the enzymatic removal of the C-terminal tyrosine of α-tubulin on assembled microtubules and the re-ligation of tyrosine on detyrosinated tubulin dimers. This modification cycle has been implicated in cardiac disease, neuronal development, and mitotic defects. The vasohibin and microtubule-associated tyrosine carboxypeptidase enzyme families are responsible for microtubule detyrosination. Their long-sought discovery allows to review and summarise differences and similarities between the two enzymes families and discuss how they interplay with other modifications and functions of the tubulin code.


Subject(s)
Carboxypeptidases , Microtubules , Tubulin , Tyrosine , Microtubules/metabolism , Humans , Animals , Tubulin/metabolism , Tubulin/chemistry , Carboxypeptidases/metabolism , Carboxypeptidases/genetics , Carboxypeptidases/chemistry , Tyrosine/metabolism , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/chemistry , Microtubule-Associated Proteins/metabolism , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/chemistry , Protein Processing, Post-Translational
2.
Science ; 384(6697): 785-792, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38753784

ABSTRACT

In response to excessive DNA damage, human cells can activate p53 to induce apoptosis. Cells lacking p53 can still undergo apoptosis upon DNA damage, yet the responsible pathways are unknown. We observed that p53-independent apoptosis in response to DNA damage coincided with translation inhibition, which was characterized by ribosome stalling on rare leucine-encoding UUA codons and globally curtailed translation initiation. A genetic screen identified the transfer RNAse SLFN11 and the kinase GCN2 as factors required for UUA stalling and global translation inhibition, respectively. Stalled ribosomes activated a ribotoxic stress signal conveyed by the ribosome sensor ZAKα to the apoptosis machinery. These results provide an explanation for the frequent inactivation of SLFN11 in chemotherapy-unresponsive tumors and highlight ribosome stalling as a signaling event affecting cell fate in response to DNA damage.


Subject(s)
Apoptosis , DNA Damage , Protein Biosynthesis , Ribosomes , Tumor Suppressor Protein p53 , Humans , Cell Line, Tumor , Codon/genetics , Leucine/genetics , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Ribosomes/metabolism , Signal Transduction , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , MAP Kinase Kinase Kinases/genetics , MAP Kinase Kinase Kinases/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL