Unknown

Dataset Information

0

K48-linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression.


ABSTRACT: T-cell proliferation is regulated by ubiquitination but the underlying molecular mechanism remains obscure. Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase. Mule is elevated in T cells upon TCR engagement, and Mule deficiency in T cells blocks proliferation because KLF4 accumulates and drives upregulation of its transcriptional targets E2F2 and the cyclin-dependent kinase inhibitors p21 and p27. T-cell-specific Mule knockout (TMKO) mice develop exacerbated experimental autoimmune encephalomyelitis (EAE), show impaired generation of antigen-specific CD8+ T cells with reduced cytokine production, and fail to clear LCMV infections. Thus, Mule-mediated ubiquitination of the novel substrate KLF4 regulates T-cell proliferation, autoimmunity and antiviral immune responses in vivo.

SUBMITTER: Hao Z 

PROVIDER: S-EPMC5241832 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

altmetric image

Publications


T-cell proliferation is regulated by ubiquitination but the underlying molecular mechanism remains obscure. Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase. Mule is elevated in T cells upon TCR engagement, and Mule deficiency in T cells blocks proliferation because KLF4 accumulates and drives upregulation of its transcriptional targets E2F2 and the cyclin-dependent kinase inhibitors p21 and p27. T  ...[more]

Similar Datasets

| S-EPMC6972862 | biostudies-literature
| S-EPMC5295445 | biostudies-literature
| S-EPMC2718286 | biostudies-literature
| S-EPMC7859282 | biostudies-literature
| S-EPMC7895832 | biostudies-literature
| S-EPMC10593845 | biostudies-literature
| S-EPMC3518595 | biostudies-literature
| S-EPMC4957694 | biostudies-literature
| S-EPMC10070438 | biostudies-literature
| S-EPMC7116596 | biostudies-literature