Disease relevance of CAND1

• On the other hand, in P19 mouse embryonal carcinoma cells, TIP120A expression was elevated upon retinoic acid treatment, which induces differentiation [1].
• In addition, a cervical intraepithelial neoplasia grade 2 lesion was shown to harbour HPV type HAN2294 (cand HPV 87) [2].
• Trichosporon cutaneum fungemia in patients with acute myeloblastic leukemia and measurement of serum D-arabinitol, Candida antigen (CAND-TEC), and beta-D-glucan [3].
• HIV Coinfection with Hepatitis Cand Hepatitis B [4].

High impact information on CAND1

• At one end, a Cand1 beta hairpin protrusion partially occupies the adaptor binding site on Cul1, inhibiting its interactions with the Skp1 adaptor and the substrate-recruiting F box protein subunits [5].
• Cand1, a 120 kDa HEAT repeat protein, forms a tight complex with the Cul1-Roc1 SCF catalytic core, inhibiting the assembly of the multisubunit E3 complex [5].
• Deletion analysis demonstrated that a 412-residue N-terminal domain, which includes an acidic region and the TBP-binding domain, is required for TIP120 function [6].
• Interestingly, TIP120 also stimulates RNAP I- and III-driven transcription and binds to RPB5, one of the common subunits of the eukaryotic RNA polymerases, in vitro [6].
• Our x-ray crystallographic studies of the C-terminal domain of FANCF reveal a helical repeat structure similar to the Cand1 regulator of the Cul1-Rbx1-Skp1-Fbox(Skp2) ubiquitin ligase complex [7].

Biological context of CAND1

• Our study suggests that, contrary to an early assumption, TIP120A is involved in tissue-specific and/or differentiation-related gene expression [1].
• The entire cDNA sequence of TIP120 contained an open reading frame encoding a novel polypeptide of 1230 amino acids [8].
• Gene expression of TIP120A in the rat liver was not stimulated by hepatocarcinogenesis or liver regeneration [1].
• Upregulation of cytochrome cand AIF immunoreactivity was noted [9].

Anatomical context of CAND1

• In a search for proteins involved in regulation of cullin-containing E3 ubiquitin ligases we immunopurified CUL4B-containing complex from HeLa cells and identified TIP120A as an associated protein by mass spectrometry [10].
• TIP120A transcripts were expressed abundantly in the heart and liver, moderately in the brain and skeletal muscle, and only slightly in the spleen and lung [1].
• Biochemical and co-transfection studies revealed that TIP120B, but not the closely related protein TIP120A, is a specific substrate of KIAA10 in vitro and within C2C12 myoblasts but not in Cos-1 cells [11].
• We found that TIP120B gene was induced in C2C12 myoblasts when these cells differentiated into myotubes, whereas TIP120A gene expression was down-regulated [12].
• The highest extent of information relevant to the discrimination between patients and normal subjects is obtained following stimulation of lymphocytes with Cand and in decreasing order with PPD, SK-SD and PHA [13].

Associations of CAND1 with chemical compounds

• Arabidopsis ETA2, an apparent ortholog of the human cullin-interacting protein CAND1, is required for auxin responses mediated by the SCF(TIR1) ubiquitin ligase [14].
• The level of TIP120A was also elevated in such stem-like cells as F9 and HL60 after each differentiation procedure, retinoic acid and DMSO, respectively [1].
• Using histidine-tagged TBP as a ligand for affinity-purification of proteins bound to TBP, we purified a 120-kD protein, termed TBP-interacting protein 120 (TIP120), from rat liver nuclear extracts [8].
• TIP120A binds to TBP in the acidic amino acid-rich N-terminal region and in the leucine-rich C-terminal region [15].
• These effects of L-NMMA were not affected significantly by pretreatment with CAND [16].

Physical interactions of CAND1

• Previous biochemical studies of CAND1 have suggested that it specifically binds to unmodified CUL1 to negatively regulate SCF assembly [14].

Enzymatic interactions of CAND1

• TIP120A greatly reduced the ubiquitination of phosphorylated IkappaBalpha by SCF(beta-TrCP) ubiquitin ligase [10].

Other interactions of CAND1

• Suppression of CAND1 in vivo increased the level of the CUL1-SKP1 complex [17].
• Furthermore, TIP120A was shown to interact selectively with Cul1 that is not modified by NEDD8 [18].

Analytical, diagnostic and therapeutic context of CAND1

• Immunoprecipitation of cullins revealed that all cullins tested specifically interacted with TIP120A [10].
• Electrophoretic mobility shift assays showed that TIP120 enhanced PIC formation, and TIP120 also stimulated the nonspecific transcription and DNA-binding activity of RNAP II [6].
• If the 1:8 titer for the colonized patient with a contaminated arterial line is not considered a false-positive result, the CAND-TEC sensitivity was 83% [19].
• GST pull-down and yeast two-hybrid assays demonstrated that hNOT3L is associated with TIP120B but not with TIP120A [12].
• To determine the timing to initiate antifungal chemotherapy, we performed the CAND-TEC assay serially in each patient [20].

References