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Fragile histidine triad protein: structure, function, and its association with tumorogenesis

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Abstract

Background

The human fragile histidine triad (FHIT) gene is a putative tumor suppressor gene, which is located at chromosome region 3p14.2. It was suggested that the loss of heterozygosity (LOH), homozygous deletions, and abnormal expression of the FHIT gene were involved in several types of human malignancies.

Materials and methods

To determine the role of FHIT in various cancers, we have performed structural and functional analysis of FHIT in detail.

Results and discussion

The protein FHIT catalyzes the Mg2+ dependent hydrolysis of P1-5¢-O-adenosine-P3-5¢-O-adenosine triphosphate, Ap3A, to AMP, and ADP. The reaction is thought to follow a two-step mechanism. Histidine triad proteins, named for a motif related to the sequence H-¢-H-¢-H-¢-¢- (¢, a hydrophobic amino acid), belong to superfamily of nucleotide hydrolases and transferases. This enzyme acts on the R-phosphate of ribonucleotides, and contain a ~30-kDa domain that is typically a homodimer of ~15 kDa polypeptides with catalytic site.

Conclusion

Here we have gathered information is known about biological activities of FHIT, the structural and biochemical bases for their functions. Our approach may provide a comparative framework for further investigation of FHIT.

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Acknowledgments

MIH is thankful to the Department of Science and Technology (DST) for the fellowship. FA is thankful to the Council of Scientific and Industrial Research and DST for the grant.

Conflict of interest statement

There is no conflict of interest for any of the authors including any financial, personal or other relationships with other people or organizations within 3 years of beginning the work submitted that could inappropriately influence the work.

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  1. Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India

    Md. Imtaiyaz Hassan, Abdullah Naiyer & Faizan Ahmad

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  1. Md. Imtaiyaz Hassan
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  2. Abdullah Naiyer
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  3. Faizan Ahmad
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Correspondence to Faizan Ahmad.

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Hassan, M.I., Naiyer, A. & Ahmad, F. Fragile histidine triad protein: structure, function, and its association with tumorogenesis. J Cancer Res Clin Oncol 136, 333–350 (2010). https://doi.org/10.1007/s00432-009-0751-9

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