Table 2 Proteins that interact with Jab1/CSN5

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]