Disease relevance of HIP2

• Adenovirus ubiquitin-protein ligase stimulates viral late mRNA nuclear export [1].
• Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer [2].
• In vitro and in vivo, forced expression of UCP boosts tumor-cell proliferation, invasion and metastasis through effects on the pVHL-HIF pathway [3].
• UCP is detected coincidently with HIF-1alpha in human primary liver, colon and breast tumors, and metastatic cholangiocarcinoma and colon cancer cells [3].
• 2. Fetal weights were less than those reported by Widdowson (1968) for similar gestational ages and the deficits were greater in LIG [4].

High impact information on HIP2

• UCP level correlates inversely with pVHL level in most tumor cell lines [3].
• The human ubiquitin carrier protein E2(Mr = 17,000) is homologous to the yeast DNA repair gene RAD6 [5].
• DNA LIG k becomes adenylated in reactions with ATP, and the adenylate moiety is removed by incubation with pyrophosphate or nicked DNA [6].
• The role of ER stress in dopaminergic neuronal vulnerability was highlighted by their decreased survival in mice deficient in the ubiquitin-protein ligase Parkin and the ER chaperone ORP150 (150 kDa oxygen-regulated protein) [7].
• Intact UCRP supports a low rate of ubiquitin-activating enzyme (E1)-dependent ATP:PPi exchange but fails to form a stoichiometric E1-UCRP thiol ester or undergo transfer to ubiquitin carrier protein (E2) [8].

Chemical compound and disease context of HIP2

• 1. Studies were made on the vitamin E status of the newborn as judged by cord serum vitamin E and erythrocyte haemolysis in vitro in relation to gestational age, birth weight and maternal vitamin E status in subjects belonging to low (LIG)- and high (HIG)-income groups in urban Baroda [9].
• Ubiquitin-protein ligase parkin and its role in the development of Parkinson's disease [10].
• RESULTS AND DISCUSSION: From the CH fragments, 2-furfural in TCF, and from the LIG fragments, styrene in ECF showed the highest probabilities of originating from source structures of toxicity [11].

Biological context of HIP2

• Ubiquitination of multiple intracellular proteins was observed in agLDL-treated macrophages, which coincided with upregulation of LIG [12].
• The dominant-negative cullin 5 protein stabilized p53 and the MRN complex, indicating that it inhibited the viral ubiquitin-protein ligase but had no effect on viral early mRNA synthesis, early protein synthesis, or viral DNA replication [1].
• This unique post-translational modification is thought to be distinct from similar cytosolic reactions in requiring ubiquitin-activating enzyme (E1) and one or more putative ubiquitin carrier proteins (E2) but not isopeptide ligase (E3) [13].
• The patterns of extracellular enzyme activities and mnp and cbh gene expression are similar whereas LIG gene expression can be detected when no corresponding enzyme activity is observed in the extracellular supernatant [14].
• 3. The combined mean values (microgram/l) for maternal serum retinol for all gestational ages were 193 for LIG and 261 for HIG [4].

Anatomical context of HIP2

• These results suggest that LIG acts as a direct mediator of foam cell formation through polyubiquitination and subsequent degradation of cellular proteins with apoptosis-inducing properties [12].
• E2-25K (Hip2), an ubiquitin-conjugating enzyme, interacts directly with huntingtin and may mediate ubiquitination of the neuronal intranuclear inclusions in Huntington disease [15].
• To determine if the ability of E1B-55K and E4orf6 to stimulate viral late mRNA nuclear export requires the ubiquitin-protein ligase activity of this viral ubiquitin-protein ligase complex, we designed and expressed a dominant-negative mutant form of cullin 5 in HeLa cells before infection with wild-type Ad5 or the E1B-55K null mutant dl1520 [1].
• Suppression of Nedd4 expression with siRNA resulted in an accumulation of gap junction plaques at the plasma membrane, suggesting an involvement of the ubiquitin protein ligase Nedd4 in gap junction internalization [16].
• Lactobin (LIG) is quite resistant to 24-h incubation with gastric juice [17].

Associations of HIP2 with chemical compounds

• In this study, we investigated the effects of the Class Ic antiarrhythmic agent flecainide (FLEC) on ionic current (I(HERG)) mediated by cloned HERG channels at 37 degrees C. We also compared the inhibitory potency of FLEC with other Class I agents: quinidine (QUIN, Class Ia); lignocaine (LIG, Class Ib) and propafenone (PROPAF, Class Ic) [18].
• 2. In the case of full-term infants, the mean values for maternal serum vitamin E (mg/l) for LIG (n 73) and HIG (n 43) were 9.9 (SE 0.4) and 11.6 (SE 0.5) [9].
• 4. Fetal liver retinol concentrations were much lower than those reported for healthy Thai subjects by Montreewasuwat & Olson (1979) in early pregnancy but showed complete 'catch up' in late pregnancy for HIG and to a considerable extent for LIG [4].
• Trabeculae were isolated from rabbits with coronary ligation-induced heart failure (LIG, n = 11), sham operated controls (SH, n = 10), isoprenaline-infused rabbits (ISO, 7 days mini-osmotic pump 100 micrograms/kg.h; n = 7) and saline-infused controls (SAL, n = 7) [19].
• By either transient or stable transfection of Chinese hamster ovary (CHO) Tet-On cells, we successfully expressed, detected, and immobilized biotinylated human Itch, a pleiotropic multi-domain ubiquitin-protein ligase, as well as Gla-RTK, a putative vitamin K-dependent receptor tyrosine kinase [20].

Physical interactions of HIP2

• Mutations in the RING domain of RNF2 prevented the clone from binding to Hip-2, an indication that the RING domain is the binding determinant [21].

Enzymatic interactions of HIP2

• Mdm2 is a ubiquitin-protein ligase known to ubiquitinate p53, promoting its degradation by the ubiquitin-proteasome system [22].

Other interactions of HIP2

• The interaction of Hip-2 with RNF2, one of the clones, was further confirmed through in vitro and in vivo experiments [21].
• Pirh2, a recently identified ubiquitin-protein ligase, has been reported to promote p53 degradation [23].
• The ubiquitin-protein ligase activity of Hdm2 is inhibited by nucleic acids [24].
• Mutations in the Ubiquitin protein ligase 3A gene (UBE3A) have been found in the latter group, but only preliminary figures are available on their frequencies [25].

Analytical, diagnostic and therapeutic context of HIP2

• Sequence analyses showed that, with one exception, all Hip-2-interacting proteins contained the RING finger motifs [21].
• The results, before and after adjustment of physical characteristics, showed that anthropometry, body composition, and lung functions were significantly higher in HIG compared to MIG and LIG children, while in girls, no differences were observed in physical characteristics after adjustments [26].
• In a multi-center pilot study 37 immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2 patients with common variable immunodeficiency (CVID), one unidentified immunodeficiency, five patients with graft versus host disease (GvHD) following bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days) [17].
• E2-EPF ubiquitin carrier protein (UCP) is a member of an E2 family of enzymes that catalyzes the ligation of ubiquitin to proteins targeted for destruction by the proteasome [27].

References