Isolation of a novel gene mutated in Wiskott-Aldrich syndrome

doi:10.1016/0092-8674(94)90528-2

Cell

Volume 78, Issue 4, 26 August 1994, Pages 635-644

https://doi.org/10.1016/0092-8674(94)90528-2 Get rights and content

Abstract

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, and recurrent infections. Linkage studies have placed the gene at Xp11.22-p11.23. We have isolated from this interval a novel gene, WASP, which is expressed in lymphocytes, spleen, and thymus. The gene is not expressed in two unrelated WAS patients, one of whom has a single base deletion that produces a frame shift and premature termination of translation. Two additional patients have been identified with point mutations that change the same arginine residue to either a histidine or a leucine. WASP encodes a 501 amino acid proline-rich protein that is likely to be a key regulator of lymphocyte and platelet function.

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As patients continue to suffer from lymphoproliferative and myeloproliferative diseases known as haematopoietic malignancies can affect the bone marrow, blood, lymph nodes, and lymphatic and non-lymphatic organs. Despite advances in the current treatment, there is still a significant challenge for physicians to improve the therapy of HMs. WASp is an important regulator of actin polymerization and the involvement of WASp in transcription is thought to be linked to the DNA damage response and repair. In some studies, severe immunodeficiency and lymphoid malignancy are caused by WASp mutations or the absence of WASp and these mutations in WAS can alter the function and/or expression of the intracellular protein. Loss-of-function and Gain-of-function mutations in WASp have an impact on cancer malignancies' incidence and onset. Recent studies suggest that depending on the clinical or experimental situation, WASPs and WAVEs can operate as a suppressor or enhancers for cancer malignancy. These dual functions of WASPs and WAVEs in cancer likely arose from their multifaceted role in cells that could be targeted for anticancer drug development. The significant role and their association of WASp in Chronic myeloid leukaemia, Juvenile myelomonocytic leukaemia and T-cell lymphoma is discussed. In this review, we described the structure and function of WASp and its family mechanism, analysing major regulatory effectors and summarising the clinical relevance and drugs that specifically target WASp in disease treatment in various hematopoietic malignancies by different approaches.
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Cell

Isolation of a novel gene mutated in Wiskott-Aldrich syndrome

Abstract

J. Pediatr.

Trends Biochem. Sci.

Blood

Blood

Lancet

Genomics

Cell

Genomics

Genomics

J. Biol. Chem.

Cell

Genomics

Genomics

J. Mol. Biol.

Genomics

Cell

Cell

Blood

Cell

Cell

Disorders of the T-cell system

Identification of a protein that binds to the SH3 region of AN and is similar to Bcr and GAP-Rho

Science

Proteins

Close linkage of hypervariable marker DXS255 to disease locus of Wiskott-Aldrich syndrome

Lancet

hnRNP proteins and the biogenesis of mRNA

Annu. Rev. Biochem.

Transcriptional activation modulated by homopolymeric glutamine and proline stretches

Science

The cell type-specific octamer transcription factor OTF-2 has two domains required for the activation of transcription

EMBO J.

Carrier detection in Wiskott-Aldrich syndrome: combined use of M27 beta for X-inactivation studies and as a linked probe

J. Pediatr.