dic(9;17)(p13;q11) PAX5/TAOK1

2014-04-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

Acute lymphoblastic leukemia (ALL)

Epidemiology

Only one case to date, a 3-year old girl with a pre-B-ALL (Coyaud et al., 2010).

Genes Involved and Proteins

Gene name
PAX5 (paired box gene 5)
Location
9p13.2
Protein description
391 amino acids; from N-term to C-term, PAX5 contains: a paired domain (aa: 16-142); an octapeptide (aa: 179-186); a partial homeodomain (aa: 228-254); a transactivation domain (aa: 304-359); and an inhibitory domain (aa: 359-391). Lineage-specific transcription factor; recognizes the concensus recognition sequence GNCCANTGAAGCGTGAC, where N is any nucleotide. Involved in B-cell differentiation. Entry of common lymphoid progenitors into the B cell lineage depends on E2A, EBF1, and PAX5; activates B-cell specific genes and repress genes involved in other lineage commitments. Activates the surface cell receptor CD19 and repress FLT3. Pax5 physically interacts with the RAG1/RAG2 complex, and removes the inhibitory signal of the lysine-9-methylated histone H3, and induces V-to-DJ rearrangements. Genes repressed by PAX5 expression in early B cells are restored in their function in mature B cells and plasma cells, and PAX5 repressed (Fuxa et al., 2004; Johnson et al., 2004; Zhang et al., 2006; Cobaleda et al., 2007; Medvedovic et al., 2011). , TAOK1 is a serine/threonine-protein kinase. TAOK1 has the ability to phosphorylate MARK1 (MAP/Microtubule affinity-regulating kinase 1, 1q41), a kinase regulating microtubule dynamics and cell polarity (Timm et al., 2003). TAOK1 regulates apoptotic morphology via C-Jun N-terminal kinases (MAPK8, 10q11.22; MAPK9, 5q35.3; MAPK10, 4q21.3) and ROCK1 (Rho-associated, coiled-coil containing protein kinase 1, 18q11.1) (Zihni et al., 2006). TAOK1 alters actin cytoskeletal organization and binds to microtubules, regulating their organization and stability (Zihni et al., 2006). The TAO kinases (TAOK1; TAOK2, 16p11.2; TAOK3, 12q24.23) mediate the activation of p38 (MAPK11, 22q13.33; MAPK12, 22q13.33; MAPK13, 6p21.31; MAPK14, 6p21.31) in response to various genotoxic stimuli. ATM (ataxia telangiectasia mutated, 11q22.3) phosphorylates the TAO kinases. TAO kinases are regulators of p38-mediated responses to DNA damage and are intermediates in the activation of p38 by ATM (Hutchison et al., 1998; Raman et al., 2007). TESK1 (testis-specific kinase 1, 9p13.3) binds to and inhibits TAOK1. The elevation of TAOK1 results in microtubule disruption. SPRED1 (sprouty-related, EVH1 domain containing 1, 15q14) - TESK1 binding causes inhibition of TESK1, making F-actin fibers dynamic (Johne et al., 2008). Taok1 controls epithelial morphogenesis by promoting Fas2 (Fasciclin 2, the insect homologue of NCAM1 (neural cell adhesion molecule 1, 11q23.2)) endocytosis in Drosophila melanogaster (Gomez et al., 2012).
Gene name
TAOK1 (TAO kinase 1)
Location
17q11.2
Protein description
1001 amino acids (aa); from N-term to C-term, TAOK1 contains: a protein kinase domain (aa 28-281), a nucleotide binding site (aa 34-42), a poly-Glu stretch (aa 330-334), a Ser-rich region (aa 347-379), and coiled coil domains (aa 458-651; 754-877). Phosphorylation on Ser/Thr followed by Gln are the following: SQ motifs: aa 363-364; 554-555; 990-991, TQ motifs: aa 502-503; 643-644; 785-786 (Raman et al., 2007).

Result of the Chromosomal Anomaly

Description

Fusion of PAX5 exon 5 to TAOK1 intron 19-20, but in reverse orientation. Transcript with exon 1B to exon 5 of PAX5, and an additional sequence of 54 bp.
Atlas Image
PAX5-TAOK1 translocation protein.

Description

Predicted fusion protein of 218 amino acids. The predicted fusion protein contains the DNA binding paired domain of PAX5 (201 aa) and 17 amino acids.

Bibliography

Pubmed IDLast YearTitleAuthors
174404522007Pax5: the guardian of B cell identity and function.Cobaleda C et al
201601642010Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study.Coyaud E et al
150040082004Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene.Fuxa M et al
232669572012Tao controls epithelial morphogenesis by promoting Fasciclin 2 endocytosis.Gomez JM et al
97868551998Isolation of TAO1, a protein kinase that activates MEKs in stress-activated protein kinase cascades.Hutchison M et al
182162812008Spred1 and TESK1--two new interaction partners of the kinase MARKK/TAO1 that link the microtubule and actin cytoskeleton.Johne C et al
152585792004B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.Johnson K et al
219709552011Pax5: a master regulator of B cell development and leukemogenesis.Medvedovic J et al
173961462007TAO kinases mediate activation of p38 in response to DNA damage.Raman M et al
145172472003MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK/PAR-1.Timm T et al
166801442006Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes.Zhang Z et al
164073102006Prostate-derived sterile 20-like kinase 2 (PSK2) regulates apoptotic morphology via C-Jun N-terminal kinase and Rho kinase-1.Zihni C et al

Summary

Fusion gene

PAX5/TAOK1 PAX5 (9p13.2) TAOK1 (17q11.2) M t(9;17)(p13;q11)

Citation

Jean-Loup Huret

dic(9;17)(p13;q11) PAX5/TAOK1

Atlas Genet Cytogenet Oncol Haematol. 2014-04-01

Online version: http://atlasgeneticsoncology.org/haematological/1598/dic(9;17)(p13;q11)

External Links