Disease relevance of TRIP10

• Our data suggest that CIP4 accumulation and cellular toxicity may have a role in HD pathogenesis [1].
• Splicing variant of Cdc42 interacting protein-4 disrupts beta-catenin-mediated cell-cell adhesion: expression and function in renal cell carcinoma [2].
• These results indicate that CIP4 is critical for beta-catenin-mediated cell-cell adhesion and may be an important aspect of its functional contribution to RCC, especially with regard to metastasis and invasiveness [2].
• We have isolated a novel human cDNA coding for human salt-tolerant protein (HSTP), that is a homologue of the rat salt-tolerant protein (STP) and may contribute to salt-induced hypertension by modulating renal cation transport [3].
• Although KSHV and HVS are related members of the rhadinovirus subgroup of gamma herpesviruses, K1 and STP exhibit no similarity in amino acid sequence or in structural organization [4].

Psychiatry related information on TRIP10

• Cdc42-interacting protein 4 binds to huntingtin: neuropathologic and biological evidence for a role in Huntington's disease [1].

High impact information on TRIP10

• At a position equivalent to the gene encoding the saimiri transforming protein (STP) of herpesvirus saimiri (HVS), Kaposi's sarcoma-associated herpesvirus (KSHV) contains a distinct open reading frame called K1 [4].
• Furthermore, knockdown of endogenous FBP17 and CIP4 impaired endocytosis [5].
• The TC10-interacting protein CIP4/2 is required for insulin-stimulated Glut4 translocation in 3T3L1 adipocytes [6].
• CIP4/2 localizes to an intracellular compartment under basal conditions and translocates to the plasma membrane on insulin stimulation [6].
• Like CIP4, Felic associated with Cdc42 in its activated form only [7].

Chemical compound and disease context of TRIP10

• These results provide evidence that combined therapy with furosemide and albumin is effective in augmenting serum albumin and STP levels, promoting weight loss, and improving oxygenation and longer-term hemodynamic stability [8].

Biological context of TRIP10

• We have identified an alternative splicing variant in the Cdc42-interacting protein 4 (CIP4) gene in patients with renal cell carcinoma (RCC); almost 50% of the RCCs examined showed an aberrant splicing event in reverse transcription-PCR and the insertion of 19 nucleotides derived from intron9 based on a sequence analysis [2].
• The nucleotide sequence (1988bp) of the HSTP cDNA contains an open reading frame encoding a polypeptide comprising 545 amino acids, two residues fewer than the rat STP cDNA [3].
• We have mapped the HSTP gene to human chromosome 19 by fluorescence in situ hybridization [3].
• Unlike CIP4, Felic does not possess a C-terminal SH3 domain [7].
• Transient transfections of RICH-1 indicated that it bound to CIP4 in vivo, as shown by co-immunoprecipitation experiments, as well as co-localization assays [9].

Anatomical context of TRIP10

• We conclude that CIP4 can mediate the association of WASP with microtubules [10].
• Co-expression of CIP4 and green fluorescent protein-WASP in COS-7 cells led to the association of WASP with microtubules [10].
• Consistently, macrophages microinjected with CIP4 constructs deficient in either the microtubule- or the WASp-binding domain also fail to reassemble podosomes [11].
• Overexpression of Felic or CIP4 inhibited NIH 3T3 cell invasiveness in a Matrigel assay [7].
• Together, these findings suggest that CIP4 may act as a link between Cdc42 signalling and regulation of the actin cytoskeleton [12].

Associations of TRIP10 with chemical compounds

• In vitro experiments showed that CIP4 binds to microtubules via its NH(2) terminus [10].
• This polyproline domain is thought to link WASp to microtubules via CDC42 interacting protein 4 (CIP4) [11].
• These data suggest that CIP4/2 may play an important role in insulin-stimulated glucose transport as a downstream effector of TC10 [6].
• The amino terminus of CIP4 bears resemblance to the non-kinase domain of the FER and Fes/Fps family of tyrosine kinases [12].
• CIP4 levels are modified by all-trans-retinoic acid [13].

Physical interactions of TRIP10

• Deletion of the Cdc42-binding domain of CIP4 did not affect the colocalization of WASP with microtubules in vivo [10].
• Cdc42-interacting protein 4 mediates binding of the Wiskott-Aldrich syndrome protein to microtubules [10].
• We found that the WASP-CIP4 interaction is mediated by the binding of the Src homology 3 domain of CIP4 to the proline-rich segment of WASP [10].
• DAAM1 was shown to bind to the SH3 domain of CIP4 in vivo [14].
• We report here the identification of the TC10-interacting protein CIP4/2 (Cdc42-interacting protein 4/2) as an effector in this pathway [6].

Regulatory relationships of TRIP10

• CIP4 binds to activated Cdc42 in vitro and in vivo and overexpression of CIP4 in Swiss 3T3 fibroblasts reduces the amount of stress fibres in these cells [12].

Other interactions of TRIP10

• FNBP1L (547 aa) showed 59.4 and 55.4% total-amino-acid identity with FNBP1 and TRIP10, respectively [15].
• Marked CIP4 overexpression also was observed in Western blot from human HD brain striatum [1].
• CIP4, like WASP, is a Cdc42 effector protein involved in cytoskeletal organization [10].
• Overexpression of mutant forms of CIP4/2 containing an N-terminal deletion or with diminished TC10 binding inhibits insulin-stimulated Glut4 translocation [6].
• Similar LexA fusions to Trip9 and Trip10 had no transcriptional activity on their own but, when coexpressed with both TR and RXR, conferred T3-dependent activation to a reporter gene controlled by LexA binding sites [16].

Analytical, diagnostic and therapeutic context of TRIP10

• Southern blotting for CIP4/Felic of genomic DNA shows a single band, suggesting no gene duplication [13].
• The results of the microarray analysis indicated that the increased expression of cdc42-interacting protein 4, KIAA0554 and tropomyosin 1, which are all associated with the cytoskeletal system, may be involved in the reduction of motile and invasive activity by the HOXD3-antisense gene transduction [17].
• Immunohistochemistry using an anti-rat STP antibody demonstrated the presence of STP immunoreactivity in the proximal tubules [18].
• Reduction in serum total protein (STP) has been shown, in a recent retrospective analysis of data from a sepsis patient population with a high frequency of ARDS, to be highly predictive of positive fluid balance, weight gain, development of ARDS, prolonged mechanical ventilation, and mortality [8].
• Immunoblotting of IR-STP from patients from healthy donors produced a diffuse band between 68 and 105 kDal and a clear narrow band at 43 kDal [19].

References