Identification of ANKRD11 as a p53 coactivator

Neilsen, Paul M.; Cheney, Kelly M.; Li, Chia-Wei; Chen, J. Don; Cawrse, Jacqueline E.; Schulz, Renèe B.; Powell, Jason A.; Kumar, Raman Krishna; Callen, David F.

doi:10.1242/jcs.026351

Cited by 83 publications

(98 citation statements)

References 44 publications

(68 reference statements)

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“…We have previously shown the ankyrin repeat domain (ANKRD11 144-288 aa ) to directly interact with wild-type p53 (Neilsen et al, 2008). We confirmed through co-immunoprecipitation assays that ANKRD11 144-288 aa could interact with both wild-type and eight p53 hotspot mutants (Figure 6a).…”

Section: Ankrd11 Suppresses Mutant P53 Gain Of Function Je Noll Et Alsupporting

confidence: 73%

“…However, expression of wild-type p53 has been demonstrated to inhibit cell migration (Gadea et al, 2002;Roger et al, 2006). Therefore, the observation that stable ANKRD11 expression can decrease the rate of cell migration in a mutant p53-dependent manner is likely due to a restoration of wild-type-like activity to the endogenous p53 mutant, as described previously (Neilsen et al, 2008).…”

Section: Input Igg Pab1620mentioning

confidence: 55%

“…Knockdown of endogenous mutant p53 in MDA-MB-468 cells results in reduced metastasis in a mouse model (Adorno et al, 2009). Expression of ANKRD11 in MDA-MB-468 cells also significantly reduced their ability to form colonies on plastic (Neilsen et al, 2008). Furthermore, loss of ANKRD11 expression with p53 mutation defines breast cancer patients with invasive tumours and poor prognosis (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…Using a novel proteinbased approach, we have shown previously that ANKRD11 can restore normal transactivation potential to a p53 hotspot mutant in a breast cancer cell line (Neilsen et al, 2008), and represents the first endogenously expressed protein with a capacity to rescue mutant p53 function. In this study we used a panel of ecdysoneinducible cell lines in a p53-null background to express various p53 hotspot mutants to investigate cellular processes that are driven by mutant p53 GOF and which can be suppressed by ANKRD11.…”

Section: Introductionmentioning

confidence: 99%

“…Results p53 mutation and loss of ANKRD11 expression define cancer patients with poor prognosis Previously, we established that ANKRD11 could restore normal transactivation potential to the p53-R273H mutant (Neilsen et al, 2008) and thus we explored a wider role for ANKRD11 in the suppression of the oncogenic functions of mutant p53. ANKRD11 was robustly expressed in the normal breast epithelium, however was downregulated in the majority of breast tumours ( Figure 1a).…”

Section: Introductionmentioning

confidence: 99%

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Mutant p53 drives multinucleation and invasion through a process that is suppressed by ANKRD11

et al. 2011

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Mutations of p53 in cancer can result in a gain of function associated with tumour progression and metastasis. We show that inducible expression of several p53 'hotspot' mutants promote a range of centrosome abnormalities, including centrosome amplification, increased centrosome size and loss of cohesion, which lead to mitotic defects and multinucleation. These mutant p53-expressing cells also show a change in morphology and enhanced invasive capabilities. Consequently, we sought for a means to specifically target the function of mutant p53 in cancer cells. This study has identified ANKRD11 as a key regulator of the oncogenic potential of mutant p53. Loss of ANKRD11 expression with p53 mutation defines breast cancer patients with poor prognosis. ANKRD11 alleviates the mitotic defects driven by mutant p53 and suppresses mutant p53-mediated mesenchymal-like transformation and invasion. Mechanistically, we show that ANKRD11 restores a native conformation to the mutant p53 protein and causes dissociation of the mutant p53-p63 complex. This represents the first evidence of an endogenous protein with the capacity to suppress the oncogenic properties of mutant p53.

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Section: Ankrd11 Suppresses Mutant P53 Gain Of Function Je Noll Et Alsupporting

confidence: 73%

Section: Input Igg Pab1620mentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mutant p53 drives multinucleation and invasion through a process that is suppressed by ANKRD11

et al. 2011

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Acquired spherocytosis due to somatic ANK1 mutations as a manifestation of clonal hematopoiesis in elderly patients

et al. 2022

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In western countries, the main cause of acquired hemolytic anemia is autoimmune hemolytic anemia (AIHA). A few cases of acquired hemolytic membrane disorders, red blood cell (RBC) enzymatic deficiencies or thalassemia-like acquired syndromes have been described so far.Most of them occurred in patients with myelodysplatic syndrome (MDS) or myeloproliferative neoplasm (MPN). 1,2 The most frequent acquired membrane disorder is elliptocytosis associated with del20q in patients with MDS. One case of acquired spherocytosis due to a large deletion encompassing the SPTB gene has been described in a 73-year-old patient with MDS, bone marrow karyotype showing complex rearrangements on Chromosomes 5 and 14. Somatic mosaicism

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Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11

Goldenberg

Riccardi

Tessier

et al. 2016

American J of Med Genetics Pt A

143

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KBG syndrome, due to ANKRD11 alteration is characterized by developmental delay, short stature, dysmorphic facial features, and skeletal anomalies. We report a clinical and molecular study of 39 patients affected by KBG syndrome. Among them, 19 were diagnosed after the detection of a 16q24.3 deletion encompassing the ANKRD11 gene by array CGH. In the 20 remaining patients, the clinical suspicion was confirmed by the identification of an ANKRD11 mutation by direct sequencing. We present arguments to modulate the previously reported diagnostic criteria. Macrodontia should no longer be considered a mandatory feature. KBG syndrome is compatible with autonomous life in adulthood. Autism is less frequent than previously reported. We also describe new clinical findings with a potential impact on the follow-up of patients, such as precocious puberty and a case of malignancy. Most deletions remove the 5'end or the entire coding region but never extend toward 16q telomere suggesting that distal 16q deletion could be lethal. Although ANKRD11 appears to be a major gene associated with intellectual disability, KBG syndrome remains under-diagnosed. NGS-based approaches for sequencing will improve the detection of point mutations in this gene. Broad knowledge of the clinical phenotype is essential for a correct interpretation of the molecular results. © 2016 Wiley Periodicals, Inc.

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Identification of ANKRD11 as a p53 coactivator

Cited by 83 publications

References 44 publications

Mutant p53 drives multinucleation and invasion through a process that is suppressed by ANKRD11

Mutant p53 drives multinucleation and invasion through a process that is suppressed by ANKRD11

Acquired spherocytosis due to somatic ANK1 mutations as a manifestation of clonal hematopoiesis in elderly patients

Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11

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