Table 2.

Proteins that interact with Jab1/CSN5

Protein	Description	Effect of Jab1/CSN5 interaction	Overall signaling effect	References
Proteins degraded by Jab1/CSN5
p27	Cyclin-dependent kinase inhibitor and tumor suppressor	Nuclear export and degradation	Increased cellular proliferation	[8]
LHR	Lutropin/choriogonadotropin receptor	Degradation	Reproductive disorders	[38]
p53	Transcription factor and tumor suppressor	Nuclear export and degradation	Inhibit p53 tumor suppressor function	[6,107,108]
Smad 4	Co-Smad, positive regulator of TGFß signaling	Ubiquitination and degradation	Inhibit TGFß signaling	[7]
Smad 7	Inhibitory Smad, negative regulator of TGFß signaling	Nuclear export and degradation	Increase TGFß signaling	[69]
ERα	Estrogen receptor α	Degradation	Increase hormone induced transcription	[109]
West nile virus Capsid	Activates caspase-3 and caspase-9 in the apoptosis pathway	Nuclear translocation and degradation	Protective against West Nile Virus	[42]
Cyclin E	Cell cycle control, G1 to S phase	Degradation	Cell cycle	[110]
Rad9-Rad1-Hus complex	Involved in DNA damage sensing and DNA repair	Degradation	Impair DNA checkpoint and repair response to DNA damage	[70]
RUNX-3	Runt-related transcription factors	Nuclear export and degradations	Inhibition of a tumor suppressor	[111]
MIF	Cytokine with tautomerase and oxidoreductases activities	Inhibition of MIF secretion	Inhibits MIF-mediated AKT signaling	[112]
DNA topoisomerase (topo) II alpha	Enzyme that is essential for cell proliferation that segregates chromosome pairs during chromosome condensation	Degradation in a MPN dependent manner under glucose starvation	Decreased cell proliferation under stress conditions such as glucose starvation	[113]
Endothelin type A and B receptors	G protein-coupled receptors whose overexpression is correlated with chronic heart failure and in infiltrating cells of atherosclerotic lesions	Ubiquitination and degradation	Decreased Endothelin-1 induced intracellular signaling through ERK1/2	[114]
Proteins affected by Jab1/CSN5
c-Jun	Member of the AP-1 transcription factor family	Transcriptional co-activator and specificity factor	Increased transcriptional activity and cellular proliferation	[1]
Myc	Oncogenic transcription factor	Promotes transcription of MYC target genes and induces MYC ubiquitination and turnover	Activates a wound signature and induced cell proliferation and invasion in breast cancer cells	[10]
HIF-1α	Hypoxia inducible factor α	Competes with p53 for binding, stabilizes protein HIF-1α levels	Increased expression of VEGF and angiogenesis	[9,115]
HAND2	Transcription factor important for development of the heart, limbs, and neural crest-derived lineages	Enhances HAND2 DNA binding	Tissue-specific transcription	[50]
53BP1	P53 binding protein, cellular response to stress conditions	Hyperphosphorylation under stress conditions	Activation of mitotic checkpoint mechanism	[48]
Smad 5	Receptor associated Smad protein, positive regulator of TGFß signaling	Inhibits bone morphogenetic signaling	Affect matrix turnover	[116]
Brn-2	POU transcription factor, development of neocortex and neural cell lineage	Increases Brn-2 transcriptional activity	Neuronal development and neurodegenerative diseases	[49]
Bcl-3	Member of Iκ-B family, proto-oncogene, can activate or inhibit NF-κB transcription	Bridges binding between Jab1/CSN5 and NF-κB	Link NF-κB and AP-1 gene activation	[47]
E2F-1	Transcription factor important for cell cycle progression, DNA damage repair, apoptosis	Cofactor for E2F-1 dependent apoptosis, but not cell cycle entry	Enhances E2F-1 mediated apoptosis	[22]
PR, SRC-1	Progesterone receptor, steroid receptor coactivator	Stabilized PR-SRC-1 complexes	Increased transcriptional activity	[37]
SMYD3	A histone methyltransferase	Suppressed transcription of the tumor suppressor p16	Negative regulation of p16 and possible increased in hematopoietic progenitors	[86]
Cullin	Subunit of SCF ubiquitin ligases	Cleavage of NEDD8 from Cul1	Required for optimal SCF ubiquitin ligase activity	[4]
PAR-2	G protein-coupled receptor for trypsin and tryptase	Increased PAR-2 transcription	Increased AP-1 activation	[117]
MDM2	Mediates p53 degradation	Reduces MDM2 self-ubiquitination	Negative regulation of p53	[108]
TRAF-2	TNFR-associated factor 2, mediator of TNFα prosurvival response	Ubiquitination of TRAF-2	Necessary for TNF-α prosurvival signaling and MMP production	[118]
Rad51	DNA repair protein involved in homologous recombination	Increases expression through negative regulation of p53	Increased ability of cell to repair DNA	[71]
FcαRI/CD89	Receptor for IgA expressed on myeloid cells and involved in phagocytosis, Ab-dependent cellular cytotoxicity, antigen presentation, and cytokine release	Binds directly to the intracellular domain and is involved in regulating stabilization of surface expression	Decreased expression of FcαR1 and possible defective antigen recognition response	[119]
5-HT(6)R	Serotonin receptor involved in the control of mood and emotion as well as involved in neurological disorders	Reduced Jab1/CSN5 expression decreases expression and activity	Reduced signaling through 5-HT(6)R, increased c-Jun activity and enhanced cell survival under hypoxia	[120]

Abbreviations: 5-HT(6)R, serotonin 6 receptor; AP-1, activator protein ; Bcl-3, B-cell lymphoma 3-encoded protein; ERα, estrogen receptor α; FcαRI, FCalphaRI; HAND2, heart- and neural crest derivatives-expressed protein 2; HIF-1α, hypoxia inducible factor α; LHR, lutropin/choriogonadotropin receptor; MIF, macrophage migration inhibitory factor; MDM2, murine double minute; NEDD8, neural precursor cell-expressed developmentally down-regulated; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; 53BP-1, p53 binding protein 1; PAR-2, abnormal embryonic PARtitioning of cytoplasm 2; PR, Progesterone receptor; SCF, Skp1-Cullin-F-box; SRC-1, steroid receptor coactivator 1; TRAF-2, TNF receptor-associated factor 2; VEGF, vascular endothelial growth factor