Wee1like

Wee1like is a designation used for a group of protein kinases that share sequence similarity with Wee1, a regulator of the G2/M cell cycle checkpoint. Wee1like proteins are found across eukaryotes and include homologs and isoforms in different lineages, reflecting their conserved role in cell cycle control.

These proteins typically function as serine/threonine kinases that phosphorylate cyclin-dependent kinases at inhibitory sites, most notably CDK1/Cdc2, to delay entry into mitosis in response to DNA damage or replication stress. In some species, Wee1like members contribute to normal timing of the cell cycle beyond stress responses, highlighting both checkpoint and progression roles.

Wee1like proteins generally possess a catalytic kinase domain with conserved motifs and regulatory regions that modulate activity and localization. In yeast, the canonical Wee1 homolog is Swe1; in other eukaryotes, Wee1like members vary in their N- and C-terminal regions and can localize to the nucleus or cytoplasm, depending on regulatory signals.

Regulation involves upstream checkpoint signaling pathways that activate Wee1like activity after DNA damage and coordinate with Cdc25 phosphatases and 14-3-3 proteins to maintain CDK in an inhibited state. Proteasomal degradation also helps modulate Wee1like protein levels across the cell cycle.

In clinical research, inhibitors targeting Wee1 have shown activity in tumors with p53 defects by abrogating the G2 checkpoint and promoting mitotic catastrophe; such inhibitors are being evaluated in combination with DNA-damaging chemotherapy or radiotherapy. Wee1like proteins may influence similar strategies in other species and contexts.

See also: Wee1, Cdc25, CDK1.

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