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Ubiquitylation of terminal deoxynucleotidyltransferase inhibits its activity.

ABSTRACT: Terminal deoxynucleotidyltransferase (TdT), which template-independently synthesizes DNA during V(D)J recombination in lymphoid cells, is ubiquitylated by a BPOZ-2/Cul3 complex, as the ubiquitin ligase, and then degraded by the 26 S proteasome. We show here that TdT is ubiquitylated by the Cul3-based ubiquitylation system in vitro. Because TdT could also be ubiquitylated in the absence of Cul/BPOZ-2, we determined that it could also be directly ubiquitylated by the E2 proteins UbcH5a/b/c and UbcH6, E3-independently. Furthermore, the ubiquitylated TdT inhibited its nucleotidyltransferase activity.

SUBMITTER: Maezawa S

PROVIDER: S-EPMC3394778 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Ubiquitylation of terminal deoxynucleotidyltransferase inhibits its activity.

Maezawa So S Fukushima Rie R Matsushita Toyofumi T Kato Tomoyoshi T Takagaki Yoshiki Y Nishiyama Yoshihiro Y Ando Sachiko S Matsumoto Takuro T Kouda Kousuke K Hayano Takahide T Suzuki Masahiro M Koiwai Kotaro K Koiwai Osamu O

PloS one 20120711 7

Terminal deoxynucleotidyltransferase (TdT), which template-independently synthesizes DNA during V(D)J recombination in lymphoid cells, is ubiquitylated by a BPOZ-2/Cul3 complex, as the ubiquitin ligase, and then degraded by the 26 S proteasome. We show here that TdT is ubiquitylated by the Cul3-based ubiquitylation system in vitro. Because TdT could also be ubiquitylated in the absence of Cul/BPOZ-2, we determined that it could also be directly ubiquitylated by the E2 proteins UbcH5a/b/c and Ubc ...[more]

PMID: 22808041

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