Disease relevance of FEZ1

• FEZ1 and its nematode homolog are reported to represent a new protein family involved in axonal outgrowth and fasciculation [1].
• Reduced FEZ1/LZTS1 expression and outcome prediction in lung cancer [2].
• Expression of a dominant-negative mutant of E4B in rat pheochromocytoma PC12 cells resulted in inhibition of neurite extension induced either by nerve growth factor or by coexpression of FEZ1 and constitutively active PKCzeta [3].
• Identification of FEZ1 as a protein that interacts with JC virus agnoprotein and microtubules: role of agnoprotein-induced dissociation of FEZ1 from microtubules in viral propagation [4].
• We have examined and found two common regions of deletion on 8p (8p12, 8p22) in oral squamous cell carcinomas (SCC)s. The possible involvement of FEZ1/LZTS1 (FEZ1) gene, a candidate tumor suppressor gene, mapped at 8p22, was also evaluated [5].

Psychiatry related information on FEZ1

• To investigate the role of FEZ1 in schizophrenia and bipolar disorder, case-control association analyses were conducted in Japanese cohorts [6].

High impact information on FEZ1

• (see p. 11 of this issue) report that either binding of the cargo linker c-Jun N-terminal kinase-interacting protein 1 (JIP1) to the light chains (LCs) or binding of fasciculation and elongation protein zeta1 (FEZ1) to the heavy chains (HCs) is insufficient for activation but that activation occurs when both are present simultaneously [7].
• We identified fasciculation and elongation protein zeta1 (FEZ1) as a binding partner of kinesin heavy chain [8].
• The protein designated FEZ1 (fasciculation and elongation protein zeta-1) consisting of 393 amino acid residues shows a high Asp/Glu content and contains several regions predicted to form amphipathic helices [9].
• Although expression of FEZ1 alone had no effect on PC12 cells, coexpression of FEZ1 and constitutively active PKCzeta stimulated the neuronal differentiation of PC12 cells [9].
• When the constitutively active mutant of PKCzeta was used, FEZ1 was found in the cytoplasm of COS-7 cells [9].

Biological context of FEZ1

• In the course of neuronal differentiation of PC12 cells, upregulation of DISC1/FEZ1 interaction was observed as along with enhanced extension of neurites by overexpression of DISC1 [1].
• NBR1 interacts with fasciculation and elongation protein zeta-1 (FEZ1) and calcium and integrin binding protein (CIB) and shows developmentally restricted expression in the neural tube [10].
• We have now identified fasciculation and elongation protein zeta 1 (FEZ1) as a protein that interacted with JCV agnoprotein in a yeast two-hybrid screen of a human brain cDNA library [4].
• FEZ1 dimerization and interaction with transcription regulatory proteins involves its coiled-coil region [11].
• We reported previously that FEZ1 and its paralogue FEZ2 are proteins that interact with NEK1, a protein kinase involved in polycystic kidney disease and DNA repair mechanisms at the G(2)/M phase of the cell cycle [11].

Anatomical context of FEZ1

• The present study shows that DISC1 participates in neurite outgrowth through its interaction with FEZ1 [1].
• In cultured hippocampal neurons, DISC1 and FEZ1 colocalized in growth cones [1].
• Upon treatment of the cells with a PKC inhibitor, staurosporin, FEZ1 was translocated from the cytoplasm to the plasma membrane, suggesting that the cytoplasmic translocation of FEZ1 is directly regulated by the PKCzeta activity [9].
• An in vitro binding assay showed that agnoprotein interacted directly with FEZ1 and microtubules [4].

Associations of FEZ1 with chemical compounds

• By the yeast two-hybrid assay with various deletion mutants of PKC, FEZ1 was shown to interact with the NH2-terminal variable region (V1) of PKCzeta and weakly with that of PKCepsilon [9].
• Starting from benzohydroxamic acid (1) structure-activity studies led to the identification of selective inhibitors of the FEZ-1 MBL, e.g., 2,5-substituted benzophenone hydroxamic acid 17 has a K(i) of 6.1+/-0.7muM against the FEZ-1 MBL but does not significantly inhibit the IMP-1, BcII, CphA or L1 MBLs [12].

Physical interactions of FEZ1

• Here, we demonstrated the existence of DISC1 protein and identified fasciculation and elongation protein zeta-1 (FEZ1) as an interacting partner of DISC1 by a yeast two-hybrid study [1].

Other interactions of FEZ1

• The gene coding for FEZ2, a homologue of FEZ1, has also been reported in rat and human [13].
• We show that binding of JIP1 and FEZ1 to Kinesin-1 is sufficient to activate the motor for MT binding and motility [8].
• The confirmed interacting proteins include FEZ1 itself and three transcription controlling proteins (SAP30L, DRAP1, and BAF60a) [11].
• Recent studies have suggested that DISC1 plays a role in neuronal outgrowth, possibly through reported interactions with the molecules Nudel and FEZ1 [14].

Analytical, diagnostic and therapeutic context of FEZ1

• FEZ1 is highly expressed in the brain and in situ hybridization analysis of Nbr1 showed that its expression is also regulated in the murine brain during development [10].
• Northern blot analysis has revealed that FEZ1 mRNA is abundantly expressed in adult rat brain and throughout the developmental stages of mouse embryo [9].
• Differential expression of FEZ1/LZTS1 gene in lung cancers and their cell cultures [15].
• Several have proven to be potentially useful clinical targets in the prognosis and therapy of bladder cancer such as staining for p53 and gene therapy strategies such as p53 and fez1 [16].

References