Context-dependent HOX transcription factor function in health and disease

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• HOX transcription factors are crucial for determining tissue fate and organogenesis during animal development.
• Misexpression of HOX proteins can lead to homeotic transformations, altering body part identity.

Purpose of the Study:

• To explore the multifaceted roles of HOX proteins in both normal development and pathological conditions such as arthritis and cancer.
• To investigate the molecular mechanisms underlying HOX protein function, including interactions, splicing, and modifications.

Main Methods:

• Analysis of HOX protein structure, including DNA-binding homeodomains and intrinsically disordered regions.
• Examination of mutations and misexpression effects in developmental and adult disease contexts.

Main Results:

• HOX proteins regulate fundamental cellular processes like proliferation, death, migration, differentiation, and angiogenesis.
• While developmental disruptions can be lethal, some HOX-related malformations are survivable.
• In adults, HOX protein dysregulation is implicated in arthritis and cancer pathogenesis.

Conclusions:

• Mutations in both structured and disordered regions of HOX proteins can significantly impact their function in disease.
• Understanding HOX protein regulation is critical for addressing physiological and pathological conditions.