Molecular Biology of Cushing’s Disease

Liu, Ning‐Ai; Ben-Shlomo, Anat; Melmed, Shlomo

doi:10.1007/978-1-4614-0011-0_2

Cited by 2 publications

(2 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, CABLES1 could provide a link between two important molecular mechanisms disrupted in corticotropinomas: dysfunction of the CDK/cyclin-dependent cell cycle regulation and activation of the epidermal growth factor receptor (EGFR) pathway ( Fukuoka et al 2011 , Liu et al 2011 a , b ). The RAC-alpha serine/threonine-protein kinase (AKT1), one of the main effectors of EGFR, can inactivate CABLES1 by phosphorylation, neutralizing this way the regulatory effect of CABLES1 over the CDK/cyclin complexes ( Fukuoka et al 2011 , Shi et al 2015 b ).…”

Section: Discussionmentioning

confidence: 99%

Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing’s disease

Hernández-Ramírez¹,

Gam²,

Valdés³

et al. 2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

The CABLES1 cell cycle regulator participates in the adrenal–pituitary negative feedback, and its expression is reduced in corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated the presence of CABLES1 mutations/copy number variations (CNVs) and their associated clinical, histopathological and molecular features in patients with Cushing’s disease (CD). Samples from 146 pediatric (118 germline DNA only/28 germline and tumor DNA) and 35 adult (tumor DNA) CD patients were screened for CABLES1 mutations. CNVs were assessed in 116 pediatric CD patients (87 germline DNA only/29 germline and tumor DNA). Four potentially pathogenic missense variants in CABLES1 were identified, two in young adults (c.532G > A, p.E178K and c.718C > T, p.L240F) and two in children (c.935G > A, p.G312D and c.1388A > G, and p.D463G) with CD; no CNVs were found. The four variants affected residues within or close to the predicted cyclin-dependent kinase-3 (CDK3)-binding region of the CABLES1 protein and impaired its ability to block cell growth in a mouse corticotropinoma cell line (AtT20/D16v-F2). The four patients had macroadenomas. We provide evidence for a role of CABLES1 as a novel pituitary tumor-predisposing gene. Its function might link two of the main molecular mechanisms altered in corticotropinomas: the cyclin-dependent kinase/cyclin group of cell cycle regulators and the epidermal growth factor receptor signaling pathway. Further studies are needed to assess the prevalence of CABLES1 mutations among patients with other types of pituitary adenomas and to elucidate the pituitary-specific functions of this gene.

show abstract

Section: Discussionmentioning

confidence: 99%

Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing’s disease

Hernández-Ramírez¹,

Gam²,

Valdés³

et al. 2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Interestingly, CABLES1 could provide a link between two important molecular mechanisms disrupted in corticotropinomas: dysfunction of the CDK/cyclin-dependent cell cycle regulation and activation of the epidermal growth factor receptor (EGFR) pathway (Fukuoka et al 2011, Liu et al 2011a. The RAC-alpha serine/threonine-protein kinase (AKT1), one of the main effectors of EGFR, can inactivate CABLES1 by phosphorylation, neutralizing this way the regulatory effect of CABLES1 over the CDK/cyclin complexes (Fukuoka et al 2011, Shi et al 2015b.…”

Section: :8mentioning

confidence: 99%

Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing's disease

2018

EJEA

View full text Add to dashboard Cite

The CABLES1 cell cycle regulator participates in the adrenal-pituitary negative feedback, and its expression is reduced in corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated the presence of CABLES1 mutations/copy number variations (CNVs) and their associated clinical, histopathological and molecular features in patients with Cushing's disease (CD). Samples from 146 pediatric (118 germline DNA only/28 germline and tumor DNA) and 35 adult (tumor DNA) CD patients were screened for CABLES1 mutations. CNVs were assessed in 116 pediatric CD patients (87 germline DNA only/29 germline and tumor DNA). Four potentially pathogenic missense variants in CABLES1 were identified, two in young adults (c.532G > A, p.E178K and c.718C > T, p.L240F) and two in children (c.935G > A, p.G312D and c.1388A > G, and p.D463G) with CD; no CNVs were found. The four variants affected residues within or close to the predicted cyclin-dependent kinase-3 (CDK3)-binding region of the CABLES1 protein and impaired its ability to block cell growth in a mouse corticotropinoma cell 379-392

show abstract

Molecular Biology of Cushing’s Disease

Cited by 2 publications

References 86 publications

Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing’s disease

Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing’s disease

Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing's disease

Contact Info

Product

Resources

About