DeubiKuitylation: A novel DUB enzymatic activity for the DNA repair protein, Ku70

Moran Rathaus, Batya Lerrer, Haim Y. Cohen

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations

Abstract

The Ku70 protein was shown to be involved in multiple cellular pathways including DNA repair, telomere maintenance, V(D)J recombination and Bax mediated apoptosis. Yet, despite this wide spectrum of pathways, until recently the enzymatic activity of Ku70 was elusive. Recent findings demonstrate that Ku70 is associated with the proapoptotic protein Bax and possesses a deubiquitin enzyme (DUB) activity on it. These data suggest a dual role for Ku70 in apoptotic regulation; on one hand the association with Ku70 sequestered Bax away from the mitochondria and plays an antiapoptotic function. On the other hand, this association mediates and promotes Bax deubiquitylation which will block its labeling for proteasomal degradation and in this manner Ku70 will have a proapoptotic role. The exciting finding of Ku70's DUB activity opens numerous avenues for future research. Here we suggest candidate substrate proteins and indicate how the DUB activity of Ku70 on these, might affect the known Ku70's related pathways.

Original languageEnglish
Pages (from-to)1843-1852
Number of pages10
JournalCell Cycle
Volume8
Issue number12
DOIs
StatePublished - 15 Jun 2009

Bibliographical note

Funding Information:
We thank Shelley Schwarzbaum and Shoshana Naiman (BIU, Israel) and members of the Cohen lab for their helpful comments on the manuscript. This study was supported by grants from the Israeli Academy of Sciences, German-Israeli Foundation, Binational US-Israel Foundation, the Israel Cancer Association, Israel Cancer Research Fund, the Koret Foundation and the Israel Health Ministry.

Funding

We thank Shelley Schwarzbaum and Shoshana Naiman (BIU, Israel) and members of the Cohen lab for their helpful comments on the manuscript. This study was supported by grants from the Israeli Academy of Sciences, German-Israeli Foundation, Binational US-Israel Foundation, the Israel Cancer Association, Israel Cancer Research Fund, the Koret Foundation and the Israel Health Ministry.

FundersFunder number
Israel Health Ministry
Israeli Academy of Sciences
US-Israel Foundation
Koret Foundation
German-Israeli Foundation for Scientific Research and Development
Israel Cancer Association

    Keywords

    • Apoptosis
    • Bax
    • Deubiquitylation (DUB)
    • Ku70

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