AFF - AF4/FMR2 family member | Elisa - Clia - Antibody - Protein

Background

The AFF (AF4/FMR2) family member refers to a group of proteins associated with various cellular functions, particularly in the context of gene regulation and transcriptional control. The name "AFF" comes from the fusion partner of MLL (Mixed-Lineage Leukemia) in certain leukemia cases, where AFF1, also known as AF4, is one of the fusion partners. AFF1 (AF4) is a protein implicated in chromosomal translocations that result in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). It's known to be involved in transcriptional elongation and regulation. The AF4 protein itself is associated with the super elongation complex (SEC), which plays a role in regulating RNA polymerase II elongation. FMR2 gene encodes a protein that is believed to be involved in transcriptional regulation and is associated with intellectual disability. Mutations in the AFF2 gene have been linked to a condition known as FRAXE syndrome, which is characterized by intellectual disability and behavioral problems. These proteins are part of a larger network of transcriptional regulators and chromatin modifiers that control gene expression in various cellular contexts. Understanding their functions and interactions is essential for elucidating the molecular mechanisms underlying normal cellular processes and diseases such as cancer and neurodevelopmental disorders.

Protein Structure

AFF proteins share structural features that enable their function in transcriptional regulation:

• N-terminal region: Often contains domains involved in protein-protein interactions, which facilitate the formation of transcriptional complexes.
• Central region: Typically includes nuclear localization signals (NLS) that direct the proteins to the nucleus, where they exert their functions.
• C-terminal region: Contains transcriptional activation domains (TAD) that interact with other transcriptional machinery components.

Classification and Subtypes

The AFF family includes four primary members:

• AFF1: Also known as AF4 (ALL1-fused gene from chromosome 4), involved in transcriptional regulation and associated with leukemia.
• AFF2: Known as FMR2 (Fragile X mental retardation 2), mutations in this gene are linked to Fragile X syndrome.
• AFF3: Also known as LAF4 (lymphoid nuclear protein related to AF4), plays roles in transcriptional regulation in lymphoid cells.
• AFF4: Another transcriptional regulator involved in forming complex transcriptional machinery.

Function and Biological Significance

AFF proteins are involved in several crucial biological processes:

1. Transcriptional Regulation: AFF family members act as transcriptional co-activators, forming complexes with other proteins to regulate gene expression.
2. RNA Processing: These proteins are involved in RNA processing, influencing mRNA stability and splicing.
3. Neurodevelopment: AFF2, in particular, plays a significant role in neural development and cognitive function.

Interactions

1. Transcription Complexes: AFF proteins form part of the super elongation complex (SEC), which is crucial for the elongation phase of transcription by RNA polymerase II.
2. Chromatin Modifiers: They interact with various chromatin remodeling proteins, affecting the accessibility of DNA for transcription.
3. RNA Processing Proteins: AFF members interact with RNA binding proteins and splicing factors, influencing RNA processing and stability.

Clinical Significance

1. Cancer: Chromosomal translocations involving AFF1 are associated with acute lymphoblastic leukemia (ALL). These translocations create fusion proteins that disrupt normal transcriptional regulation.
2. Fragile X Syndrome: Mutations in the AFF2 gene cause Fragile X syndrome, a condition characterized by intellectual disability and developmental delays.
3. Neurodevelopmental Disorders: Alterations in the function of AFF proteins can lead to various neurodevelopmental disorders, given their role in neural development and gene expression regulation.

Summary

The AF4/FMR2 (AFF) family comprises transcriptional regulators crucial for gene expression, RNA processing, and neural development. Key members, including AFF1, AFF2, AFF3, and AFF4, are involved in forming transcriptional complexes and interacting with RNA processing machinery. Clinically, AFF1 is associated with leukemia due to chromosomal translocations, while AFF2 mutations lead to Fragile X syndrome. Understanding the roles and interactions of AFF proteins is vital for elucidating their contributions to development and disease.