Disease relevance of Mybl1

• We report here that mice homozygous for a germline mutation in A-myb develop to term but show defects in growth after birth and male infertility due to a block in spermatogenesis [1].
• After a 9-month latency, A-myb transgenic mice developed hyperplasia of the spleen and lymph nodes [2].
• A-myb rescues murine B-cell lymphomas from IgM-receptor-mediated apoptosis through c-myc transcriptional regulation [3].
• These findings suggest that the A-myb plays a role in the reactive gliosis signaling pathway in KA-induced excitotoxic lesions [4].

High impact information on Mybl1

• Morphological examination of the testes of A-myb-/- males revealed that the germ cells enter meiotic prophase and arrest at pachytene [1].
• These results demonstrate that A-myb plays a critical role in spermatogenesis and mammary gland development [1].
• In female mice, A-myb is expressed in breast ductal epithelium, mainly during pregnancy-induced ductal branching and alveolar development [1].
• Mouse A-myb maps to the proximal region of chromosome 1 and encodes a transcriptional activator with properties similar to those of the c-myb and v-myb proteins [5].
• In the adult mouse, A-myb is expressed during the early stages of sperm cell differentiation and in B lymphocytes located in germinal centers of the spleen [5].

Biological context of Mybl1

• A-myb null mutant mice, on the other hand are viable but exhibit growth abnormalities, and defects in spermatogenesis and female breast development [6].
• While the C-terminal domains of A-Myb and c-Myb proteins exert a negative regulatory effect on their transcriptional transactivation function, the C-terminal domain of B-Myb appears to function as a positive regulator of this activity [6].
• Our work provides the first evidence that the function of A-Myb is regulated by the cell cycle machinery and that the carboxy-terminal domain of A-Myb acts as a cell cycle sensor [7].
• We here show that the transactivation potential of A-Myb is repressed by the C-terminal domain and that phosphorylation of A-Myb, induced by cyclins A and E, relieves this inhibitory effect [7].
• A-myb, a conserved member of the Myb proto-oncogene family, encodes a sequence-specific DNA binding protein (A-Myb) that binds to and transactivates promoters containing myb-binding sites [7].

Anatomical context of Mybl1

• In adult male mice, A-myb is expressed predominantly in male germ cells [1].
• During embryo-genesis A-myb is predominantly expressed in several regions of the developing central nervous system (CNS) and the urogenital ridge [5].
• This pattern of expression suggests that A-myb is involved in the control of proliferation and differentiation of spermatogonia [8].
• A-myb mRNA expression increased at post-natal day 10, when primary spermatocytes first appear [9].
• Functionally, dMax reduced the ability of c-Myc to cooperate with the progression factor A-Myb to promote S phase entry of quiescent smooth muscle cells [10].

Associations of Mybl1 with chemical compounds

• Three days after KA treatment, strong A-myb immunoreactivity was observed in reactive astrocytes throughout the CA3 region [4].
• In the present study, we examined patterns of A-myb expression in the kainic acid (KA)-treated mouse hippocampus [4].

Other interactions of Mybl1

• The presence of potential phosphorylation sites for cyclin-dependent kinases in the C-terminus of A-Myb has prompted us to examine the possibility that the function of A-Myb is controlled by the cell cycle [7].
• Deletion of the COOH-terminal domain of A-Myb, or co-expression with Ets-2 resulted in increased transactivation potential [11].
• Co-expression of A-myb and ets-2 in these cells results in the restoration of the proliferative activity of the cells in G-CSF, but fails to induce a block to G-CSF-induced terminal differentiation [11].
• Comparison of the mouse, rat, and human proximal promoters revealed regions of high sequence conservation and consensus sequences both for known transcription factors, some of which are coexpressed with Ccna1, such as A-myb and Hsf2, and for elements that control expression of genes in somatic cell cycles, such as CDE, CHR, and CCAAT elements [12].

Analytical, diagnostic and therapeutic context of Mybl1

• The A-myb mRNA is detectable by in situ hybridization specifically in the spermatogenic cells, and is downregulated during terminal differentiation [9].
• Northern blot analysis of adult mouse tissue RNAs reveals A-myb expression predominantly in the testis, with very low levels of expression in the ovaries, spleen and brain [8].
• The A-myb mRNA was not detectable by in situ hybridization in fetal day 15.5 gonocytes but was detectable at a low abundance by RT-PCR in fetal and newborn mice [9].
• Western blot analysis revealed that A-myb expression was dramatically increased in brain 3 days after KA treatment, and was sustained for more than 7 days [4].

References