Protein competition switches the function of COP9 from self-renewal to differentiation

Lei Pan, Su Wang, Tinglin Lu, Changjiang Weng, Xiaoqing Song, Joseph K. Park, Jin Sun, Zhi Hao Yang, Junjing Yu, Hong Tang, Dennis M. McKearin, Daniel A. Chamovitz, Jianquan Ni, Ting Xie

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

The balance between stem cell self-renewal and differentiation is controlled by intrinsic factors and niche signals. In the Drosophila melanogaster ovary, some intrinsic factors promote germline stem cell (GSC) self-renewal, whereas others stimulate differentiation. However, it remains poorly understood how the balance between self-renewal and differentiation is controlled. Here we use D. melanogaster ovarian GSCs to demonstrate that the differentiation factor Bam controls the functional switch of the COP9 complex from self-renewal to differentiation via protein competition. The COP9 complex is composed of eight Csn subunits, Csn1-8, and removes Nedd8 modifications from target proteins. Genetic results indicated that the COP9 complex is required intrinsically for GSC self-renewal, whereas other Csn proteins, with the exception of Csn4, were also required for GSC progeny differentiation. Bam-mediated Csn4 sequestration from the COP9 complex via protein competition inactivated the self-renewing function of COP9 and allowed other Csn proteins to promote GSC differentiation. Therefore, this study reveals a protein-competition-based mechanism for controlling the balance between stem cell self-renewal and differentiation. Because numerous self-renewal factors are ubiquitously expressed throughout the stem cell lineage in various systems, protein competition may function as an important mechanism for controlling the self-renewal-to-differentiation switch.

Original languageEnglish
Pages (from-to)233-236
Number of pages4
JournalNature
Volume514
Issue number7521
DOIs
StatePublished - 9 Oct 2014
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Protein competition switches the function of COP9 from self-renewal to differentiation'. Together they form a unique fingerprint.

Cite this