Rare Diseases Symptoms Automatic Extraction

Kaposi's sarcoma-associated herpesvirus-encoded LANA can induce chromosomal instability through targeted degradation of the mitotic checkpoint kinase Bub1.

[primary effusion lymphoma]

Kaposi's sarcoma-associated herpesvirus (KSHV) has a significant contributory role in the development of three major human neoplastic or lymphoproliferative diseases: Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). These diseases are associated with chromosomal instability, a hallmark of human cancer. The latency-associated nuclear antigen (LANA) encoded by KSHV plays a key role in regulating a number of cellular pathways critical for oncogenesis. KSHV LANA alone can induce the development of B-cell hyperplasia and lymphoma in mice expressing LANA. LANA also induces chromosomal instability, thus promoting oncogenesis. However, the precise mechanism underlying LANA-mediated chromosomal instability remains uncharted. Here we report that LANA promoted the induction of chromosomal instability and the formation of micronuclei and multinucleation through its interaction with one of the critical spindle checkpoint proteins, Bub1, and the resulting degradation of Bub1. This interaction occurs through the Knl and kinase domains of Bub1, identified as important for stability and degradation. These results suggest that LANA can dysregulate Bub1 activity, which leads to aberrant chromosome replication and aneuploidy, thus contributing to KSHV-mediated oncogenesis.This work represents the first set of results identifying a novel mechanism by which LANA, a latency-associated antigen encoded by KSHV, can induce the degradation of Bub1, a spindle checkpoint protein that is important for spindle checkpoint signaling and chromosome segregation. The downregulation of Bub1 mediated by LANA resulted in chromosomal instability, a hallmark of cancer. We further investigated the specific domains of Bub1 that are required for the interaction between LANA and Bub1. The results demonstrated that the Knl and kinase domains of Bub1 are required for the interaction between LANA and Bub1. In addition, we also investigated the mechanism by which LANA promoted Bub1 degradation. Our results showed that LANA interacted physically with the anaphase-promoting complex (APC/C), thus promoting the degradation of Bub1 in a ubiquitin-dependent process.

Diseases presenting "cancer" symptom

  • achondroplasia
  • acute rheumatic fever
  • adrenal incidentaloma
  • alpha-thalassemia
  • benign recurrent intrahepatic cholestasis
  • cadasil
  • canavan disease
  • carcinoma of the gallbladder
  • cholangiocarcinoma
  • coats disease
  • congenital adrenal hyperplasia
  • congenital diaphragmatic hernia
  • cowden syndrome
  • cushing syndrome
  • cutaneous mastocytosis
  • dedifferentiated liposarcoma
  • dystrophic epidermolysis bullosa
  • epidermolysis bullosa simplex
  • erdheim-chester disease
  • erythropoietic protoporphyria
  • esophageal adenocarcinoma
  • esophageal carcinoma
  • esophageal squamous cell carcinoma
  • familial hypocalciuric hypercalcemia
  • familial mediterranean fever
  • gm1 gangliosidosis
  • heparin-induced thrombocytopenia
  • hereditary cerebral hemorrhage with amyloidosis
  • hirschsprung disease
  • hodgkin lymphoma, classical
  • inclusion body myositis
  • junctional epidermolysis bullosa
  • kabuki syndrome
  • kallmann syndrome
  • kindler syndrome
  • lamellar ichthyosis
  • liposarcoma
  • locked-in syndrome
  • lymphangioleiomyomatosis
  • monosomy 21
  • neuralgic amyotrophy
  • oculocutaneous albinism
  • oligodontia
  • oral submucous fibrosis
  • papillon-lefèvre syndrome
  • pendred syndrome
  • pleomorphic liposarcoma
  • primary effusion lymphoma
  • proteus syndrome
  • pyomyositis
  • pyruvate dehydrogenase deficiency
  • severe combined immunodeficiency
  • sneddon syndrome
  • systemic capillary leak syndrome
  • triple a syndrome
  • von hippel-lindau disease
  • waldenström macroglobulinemia
  • well-differentiated liposarcoma
  • werner syndrome
  • wiskott-aldrich syndrome
  • wolf-hirschhorn syndrome
  • x-linked adrenoleukodystrophy

This symptom has already been validated