Multiple functions of Jab1 are required for early embryonic development and growth potential in mice.
AuthorsTomoda K, Yoneda-Kato N, Fukumoto A, Yamanaka S, Kato JY,
JournalJ Biol Chem
PubMed ID15299027
'Jab1 interacts with a variety of signaling molecules and regulates their stability in mammalian cells. As the fifth component of the COP9 signalosome (CSN) complex, Jab1 (CSN5) plays a central role in the deneddylation of the cullin subunit of the Skp1-Cullin-F box protein ubiquitin ligase complex. In addition, a CSN-independent ... More
HERC2 Targets the Iron Regulator FBXL5 for Degradation and Modulates Iron Metabolism.
AuthorsMoroishi T, Yamauchi T, Nishiyama M, Nakayama KI,
Journal
PubMed ID24778179
'FBXL5 (F-box and leucine-rich repeat protein 5) is the F-box protein subunit of, and therefore responsible for substrate recognition by, the SCF(FBXL5) ubiquitin-ligase complex, which targets iron regulatory protein 2 (IRP2) for proteasomal degradation. IRP2 plays a central role in the maintenance of cellular iron homeostasis in mammals through posttranscriptional ... More
SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein.
AuthorsShirogane T, Jin J, Ang XL, Harper JW,
JournalJ Biol Chem
PubMed ID15917222
Circadian rhythms are controlled by the periodic accumulation of Period proteins, which act as transcriptional repressors of Clock-dependent genes. Period genes are themselves Clock targets, thereby establishing a negative transcriptional feedback circuit controlling circadian periodicity. Previous data have implicated the CK1epsilon isolog Doubletime (Dbt) and the F-box protein Slimb in ... More
The F-box protein SKP2 mediates androgen control of p27 stability in LNCaP human prostate cancer cells.
AuthorsLu L, Schulz H, Wolf DA,
JournalBMC Cell Biol
PubMed ID12188931
The cyclin-dependent kinase inhibitor p27 is a putative tumor suppressor that is downregulated in the majority of human prostate cancers. The mechanism of p27 down-regulation in prostate cancers in unknown, but presumably involves increased proteolysis mediated by the SCFSKP2 ubiquitin ligase complex. Here we used the human prostate cancer cell ... More
Selective enhancing effect of early mitotic inhibitor 1 (Emi1) depletion on the sensitivity of doxorubicin or X-ray treatment in human cancer cells.
AuthorsShimizu N, Nakajima NI, Tsunematsu T, Ogawa I, Kawai H, Hirayama R, Fujimori A, Yamada A, Okayasu R, Ishimaru N, Takata T, Kudo Y,
JournalJ Biol Chem
PubMed ID23645673
Chemotherapy and radiation in addition to surgery has proven useful in a number of different cancer types, but the effectiveness in normal tissue cannot be avoided in these therapies. To improve the effectiveness of these therapies selectively in cancer tissue is important for avoiding side effects. Early mitotic inhibitor 1 ... More
Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage.
AuthorsBusino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello NV, Hershko A, Pagano M, Draetta GF,
JournalNature
PubMed ID14603323
The Cdc25A phosphatase is essential for cell-cycle progression because of its function in dephosphorylating cyclin-dependent kinases. In response to DNA damage or stalled replication, the ATM and ATR protein kinases activate the checkpoint kinases Chk1 and Chk2, which leads to hyperphosphorylation of Cdc25A. These events stimulate the ubiquitin-mediated proteolysis of ... More
UBXN7 docks on neddylated cullin complexes using its UIM motif and causes HIF1a accumulation.
AuthorsBandau S, Knebel A, Gage ZO, Wood NT, Alexandru G,
JournalBMC Biol
PubMed ID22537386
The proteins from the UBA-UBX family interact with ubiquitylated proteins via their UBA domain and with p97 via their UBX domain, thereby acting as substrate-binding adaptors for the p97 ATPase. In particular, human UBXN7 (also known as UBXD7) mediates p97 interaction with the transcription factor HIF1a that is actively ubiquitylated ... More
Cullin-3 regulates late endosome maturation.
AuthorsHuotari J, Meyer-Schaller N, Hubner M, Stauffer S, Katheder N, Horvath P, Mancini R, Helenius A, Peter M
JournalProc Natl Acad Sci U S A
PubMed ID22219362
Cullin-3 (Cul3) functions as a scaffolding protein in the Bric-a-brac, Tramtrack, Broad-complex (BTB)-Cul3-Rbx1 ubiquitin E3 ligase complex. Here, we report a previously undescribed role for Cul3 complexes in late endosome (LE) maturation. RNAi-mediated depletion of Cul3 results in a trafficking defect of two cargoes of the endolysosomal pathway, influenza A ... More
SCF(FBXO22) regulates histone H3 lysine 9 and 36 methylation levels by targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal degradation.
AuthorsTan MK, Lim HJ, Harper JW
JournalMol Cell Biol
PubMed ID21768309
Reversible methylation of lysine residues has emerged as a central mechanism for epigenetic regulation and is a component of the "histone code," which engenders histones with gene regulatory information. KDM4A is a histone demethylase that targets tri- and dimethylation marks on histone H3 lysines 9 and 36. While the abundance ... More