WEE2

Alternative Name: WEE1 HOMOLOG 2; WEE1B; WEE2 Kinase

Description: WEE2 phosphorylates and inhibits CDC2, which is a catalytic subunit of metaphase promoting factor (MPF) and thus, acts as a negative regulator of oocyte maturation and fertilization. WEE2 is specifically expressed in the oocyte in mice, rhesus macaques, and humans. Inhibition of WEE2 prevents final meiotic maturation of the oocyte (metaphase II arrest) and consequently blocks fertilization.

Target

Product Details

User: Female

Hormonal: No

Role in reproduction: Oocyte Maturation

Multipurpose Preventive Technology (MPT): No

Status Details

Developer: Oregon Health & Science University, University of Minnesota

Project Phase: Discovery and Early Development

Development Stage: Lead Optimization

Began discovery in: 2008

Active Development: Yes

Status Details:
  • Studies have demonstrated sole expression of WEE2 in the oocyte in rodents and nonhuman primates. WEE2 knockdown in the oocyte leads to leaky meiotic resumption in the presence of PDE inhibitors, and over-expression of WEE2 causes delayed oocyte maturation under conditions that would otherwise induce meiotic resumption. Results suggest an inhibitory role of WEE2 downstream of cAMP in primates.
  • Verification of activity of lead inhibitors will be accomplished using oocyte culture. Positive results will lead to initial testing using nonhuman primates.

Additional Information

References:
  • Nishimura T, Shimaoka T, et al. (2009) Insufficient amount of Cdc2 and continuous activation of Wee1 B are the cause of meiotic failure in porcine growing oocytes. J Reprod Dev. 55: 553-557.

  • Hanna CB, Yao S, et al. (2010) WEE2 is an oocyte-specific meiosis inhibitor in rhesus macaque monkeys. Biology of Reproduction. 82:1190-7.

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