MYBL2

MYBL2 Full Name

v-myb avian myeloblastosis viral oncogene homolog-like 2

MYBL2 Introduction

MYBL2 (v-myb avian myeloblastosis viral oncogene homolog-like 2), also known as B-Myb, is a member of the MYB family of transcription factors and functions as a key regulator of cell proliferation, cell cycle progression, and genome stability. Unlike MYB and MYBL1, which are mainly involved in lineage-specific differentiation, MYBL2 is broadly expressed in actively dividing cells and plays an essential role in controlling the transition through the S phase and G2/M phase of the cell cycle. As a transcription factor, MYBL2 forms the Myb-MuvB (MMB) complex with MuvB core components and FOXM1 to activate genes required for mitotic entry, chromosome condensation, DNA replication, and DNA damage response. For researchers investigating cancer biology and therapeutic targets, understanding MYBL2 is particularly important because abnormal activation of this transcriptional regulator can convert a normal cell-cycle program into a driver of uncontrolled tumor growth.

At the molecular level, MYBL2 activity is tightly controlled through post-translational modifications, especially cyclin-dependent kinase (CDK)-mediated phosphorylation, which regulates its DNA-binding ability and transcriptional activity. Recent mechanistic studies have demonstrated that phosphorylation events and the negative regulatory domain of B-Myb determine its interaction with target promoters, highlighting MYBL2 as a finely tuned cell-cycle checkpoint regulator rather than a simple proliferation marker. MYBL2 also participates in multiple oncogenic signaling networks, including the YAP/MMB pathway controlling mitotic progression, the Wnt/β-catenin/MYBL2 axis involved in DNA repair regulation, and mTOR-associated growth signaling. In addition, MYBL2 interacts with other transcriptional regulators such as E2F2, forming reciprocal feed-forward regulatory loops that amplify cancer-associated gene expression programs. These findings explain why MYBL2 overexpression or dysregulation is frequently observed in aggressive tumors and why it has emerged as a potential biomarker and therapeutic target in oncology research.

Growing evidence links MYBL2 dysregulation to the development and progression of multiple human diseases, particularly cancers including colorectal cancer, breast cancer, lung cancer, gastric cancer, leukemia, and other highly proliferative malignancies. In colorectal cancer, MYBL2 has been shown to accelerate tumor progression through transcriptional cooperation with E2F2, promoting cell-cycle activation and malignant growth. In lung cancer, MYBL2 can directly regulate tumor-promoting genes such as NCAPH, while altered MYBL2 expression has also been associated with chemotherapy response, DNA repair capacity, and tumor immune regulation. Beyond cancer, MYBL2 abnormalities may contribute to disorders involving abnormal cell proliferation and genomic instability. Current research suggests that targeting MYBL2-related regulatory networks, including MYBL2 phosphorylation pathways, transcriptional partners, and upstream regulators such as microRNAs or circular RNAs, may provide new opportunities for precision medicine development. As a central transcriptional hub connecting proliferation, DNA repair, and oncogenic signaling, MYBL2 remains an important target for understanding disease mechanisms and discovering next-generation therapeutic strategies.

Alternate Names for MYBL2

MYBL2; v-myb avian myeloblastosis viral oncogene homolog-like 2; BMYB; B-MYB; myb-related protein B; myb-like protein 2; v-myb myeloblastosis viral oncogene homolog-like 2;

• 1.Wijeratne TU, et al.; Cyclin-dependent kinase-mediated phosphorylation and the negative regulatory domain of transcription factor B-Myb modulate its DNA binding. J Biol Chem. 2022, 298(9):102319.
  2.Fan X, et al.; B-Myb accelerates colorectal cancer progression through reciprocal feed-forward transactivation of E2F2. Oncogene. 2021, 40(37):5613-5625.