REGγ: A shortcut to destruction

Department of Pathology and Laboratory Medicine, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA.
Cell (Impact Factor: 32.24). 02/2006; 124(2):256-7. DOI: 10.1016/j.cell.2006.01.003
Source: PubMed


Destruction of intact cellular proteins is largely orchestrated by ATP-dependent ubiquitination and subsequent degradation by the 26S proteasome. The REG-20S proteasome, however, only degrades short peptides. In this issue of Cell, challenge this notion by revealing that the proteasomal activator REGgamma directs degradation of the steroid receptor coactivator SRC-3 by the 20S proteasome in an ATP- and ubiquitin-independent manner.

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    • "Degradation occurs in a ubiquitin-dependent manner in the AF-2 domain of PPARγ.159 However, the AF-1 domains of PPARγ1 and PPARγ2 are degraded by the REGγ proteasome, a type of proteasome that degrades the target substrate in an ubiquitin and ATP-independent fashion.159-161 "
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    • "These observations, in agreement with previous data suggesting a role for REG-c only in the degradation of short peptides, lead to the hypothesis that this pathway could be specialized for the proteasomal degradation of small unstructured proteins since p19ARF, p21, and p16 are all unstructured when not associated with specific binding partners (such as cyclins and Cdks, for p21 and p16, and nucleophosmin in the case of p19ARF). However, the fact that REG-c is involved in the ubiquitin-independent proteolysis of the oncogenic protein steroid receptor coactivator-3 (SRC-3) challenges the idea that REG-c is implicated only in the degradation of substrates with disordered elements [23] [24]. An interesting possibility is that the feature of proteins targeted to the REG-c pathway is the lack of ubiquitination, usually due to the absence of lysine residues. "
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