HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.

The emergence of drug resistance leading to cancer recurrence is one of the challenges in the treatment of cancer patients. Several mechanisms can lead to drug resistance, including epigenetic changes. Histone deacetylases (HDACs) play a key role in chromatin regulation through epigenetic mechanisms and are also involved in drug resistance.

Opitz syndrome: improving clinical interpretation of intronic variants in MID1 gene.

Background: Loss-of-function variants in MID1 are the most common cause of Opitz G/BBB syndrome (OS). The interpretation of intronic variants affecting the splicing is a rising issue in OS.

Methods: Exon sequencing of a 2-year-old boy with OS showed that he was a carrier of the de novo c.

Mutations Are Not Common in Sporadic Cases of Opitz G/BBB Syndrome.

Opitz G/BBB syndrome (OS) is a rare genetic developmental condition characterized by congenital defects along the midline of the body. The main clinical signs are represented by hypertelorism, laryngo-tracheo-esophageal defects and hypospadias. The X-linked form of the disease is associated with mutations in the gene located in Xp22 whereas mutations in the gene in 22q11 have been linked to few cases of the autosomal dominant form of this disorder, as well as to other genetic syndromes.

Microtubular TRIM36 E3 Ubiquitin Ligase in Embryonic Development and Spermatogenesis.

TRIM36 is a member of the tripartite motif (TRIM) family of RING-containing proteins, also known as Haprin, which was first discovered for its abundance in testis and found to be implicated in the spermatozoa acrosome reaction. TRIM36 is a microtubule-associated E3 ubiquitin ligase that plays a role in cytoskeletal organization, and according to data gathered in different species, coordinates growth speed and stability, acting on the microtubules' plus end, and impacting on cell cycle progression. TRIM36 is also crucial for early developmental processes, in , where it is needed for dorso-ventral axis formation, but also in humans as bi-allelic mutations in the TRIM36 gene cause a form of severe neural tube closure defect, called anencephaly.

The MID1 gene product in physiology and disease.

MID1 is an E3 ubiquitin ligase of the Tripartite Motif (TRIM) subfamily of RING-containing proteins, hence also known as TRIM18. MID1 is a microtubule-binding protein found in complex with the catalytic subunit of PP2A (PP2Ac) and its regulatory subunit alpha 4 (α4). To date, several substrates and interactors of MID1 have been described, providing evidence for the involvement of MID1 in a plethora of essential biological processes, especially during embryonic development.