TY - JOUR
T1 - DCAF1 (VprBP)
T2 - Emerging physiological roles for a unique dual-service E3 ubiquitin ligase substrate receptor
AU - Schabla, N. Max
AU - Mondal, Koushik
AU - Swanson, Patrick C.
N1 - Funding Information:
P.C.S. gratefully acknowledges support from the National Institutes of Health (NIH) (R01GM102487) and revenue from Nebraska’s excise tax on cigarettes awarded to Creighton University through the Nebraska Department of Health & Human Services (DHHS). This publication’s contents represent the views of the authors and do not necessarily represent the official views of the State of Nebraska, DHHS, or the NIH.
PY - 2019/5/8
Y1 - 2019/5/8
N2 - Cullin-RING ligases (CRLs) comprise a large group of modular eukaryotic E3 ubiquitin ligases. Within this family, the CRL4 ligase (consisting of the Cullin4 [CUL4] scaffold protein, the Rbx1 RING finger domain protein, the DNA damage-binding protein 1 [DDB1], and one of many DDB1-associated substrate receptor proteins) has been intensively studied in recent years due to its involvement in regulating various cellular processes, its role in cancer development and progression, and its subversion by viral accessory proteins. Initially discovered as a target for hijacking by the human immunodeficiency virus accessory protein r, the normal targets and function of the CRL4 substrate receptor protein DDB1-Cul4-associated factor 1 (DCAF1; also known as VprBP) had remained elusive, but newer studies have begun to shed light on these questions. Here, we review recent progress in understanding the diverse physiological roles of this DCAF1 in supporting various general and cell type-specific cellular processes in its context with the CRL4 E3 ligase, as well as another HECT-type E3 ligase with which DCAF1 also associates, called EDD/UBR5. We also discuss emerging questions and areas of future study to uncover the dynamic roles of DCAF1 in normal physiology.
AB - Cullin-RING ligases (CRLs) comprise a large group of modular eukaryotic E3 ubiquitin ligases. Within this family, the CRL4 ligase (consisting of the Cullin4 [CUL4] scaffold protein, the Rbx1 RING finger domain protein, the DNA damage-binding protein 1 [DDB1], and one of many DDB1-associated substrate receptor proteins) has been intensively studied in recent years due to its involvement in regulating various cellular processes, its role in cancer development and progression, and its subversion by viral accessory proteins. Initially discovered as a target for hijacking by the human immunodeficiency virus accessory protein r, the normal targets and function of the CRL4 substrate receptor protein DDB1-Cul4-associated factor 1 (DCAF1; also known as VprBP) had remained elusive, but newer studies have begun to shed light on these questions. Here, we review recent progress in understanding the diverse physiological roles of this DCAF1 in supporting various general and cell type-specific cellular processes in its context with the CRL4 E3 ligase, as well as another HECT-type E3 ligase with which DCAF1 also associates, called EDD/UBR5. We also discuss emerging questions and areas of future study to uncover the dynamic roles of DCAF1 in normal physiology.
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U2 - 10.1093/jmcb/mjy085
DO - 10.1093/jmcb/mjy085
M3 - Review article
C2 - 30590706
AN - SCOPUS:85074303425
VL - 11
SP - 725
EP - 735
JO - Journal of Molecular Cell Biology
JF - Journal of Molecular Cell Biology
SN - 1674-2788
IS - 9
ER -