Speeding through cell cycle roadblocks: Nuclear cyclin D1-dependent kinase and neoplastic transformation

Cell Division

Table 1 Summary of mutations targeting cyclin D1 phosphorylation or ligase function

Target	Mutation	Consequence	Tumor Type	Reference
Cyclin D1	T286R	Constitutively Nuclear	Esophageal	[18]
Cyclin D1	Δ266–295	Constitutively Nuclear	Esophageal	[18]
Cyclin D1	P287A	Constitutively Nuclear	Tumor-derived esophageal carcinoma cell lines TE3, TE7, and TE12	[18]
Cyclin D1	P287S/T	Constitutively Nuclear	Endometrial	[17]
Cyclin D1	Δ289–292	Constitutively Nuclear	Endometrial	[17]
αB crystallin	Chromosome 11 deletion	Impaired ligase activity	Tumor-derived breast cancer cell lines (MCF-7, MDA-MB 231)	[14]
Fbx4	S8R	Impaired ligase activity	Esophageal	[26]
Fbx4	S12L	Disrupts phosphorylation	Esophageal	[26]
Fbx4	P13S	Disrupts phosphorylation	Esophageal	[26]
Fbx4	L23Q	Dimerization-deficient	Esophageal	[26]
Fbx4	P76T	Impaired Skp1 binding	Esophageal	[26]

Mutations disrupting GSK3β-dependent cyclin D1 phosphorylation and nuclear export include mutation of Thr-286, Pro-287, and deletion of residues corresponding to the CRM1 binding site. Mutations targeting the SCF^{Fbx4-αB crystallin} E3 ubiquitin ligase result in impaired ligase activity and subsequent cyclin D1/CDK4 accumulation in the nucleus.

ISSN: 1747-1028