The emerging roles and therapeutic potential of cyclin-dependent kinase 11 (CDK11) in human cancer

Abstract

Overexpression and/or hyperactivation of cyclin-dependent kinases (CDKs) are common features of most cancer types. CDKs have been shown to play important roles in tumor cell proliferation and growth by controlling cell cycle, transcription, and RNA splicing. CDK4/6 inhibitor palbociclib has been recently approved by the FDA for the treatment of breast cancer. CDK11 is a serine/threonine protein kinase in the CDK family and recent studies have shown that CDK11 also plays critical roles in cancer cell growth and proliferation. A variety of genetic and epigenetic events may cause universal overexpression of CDK11 in human cancers. Inhibition of CDK11 has been shown to lead to cancer cell death and apoptosis. Significant evidence has suggested that CDK11 may be a novel and promising therapeutic target for the treatment of cancers. This review will focus on the emerging roles of CDK11 in human cancers, and provide a proof-of-principle for continued efforts toward targeting CDK11 for effective cancer treatment.

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

“…The larger 110 kDa protein isoform, CDK11 p110 , is mainly associated with RNA splicing and generates the CDK11 p58 isoform during the G 2 –M phase of the cell cycle. A 58 kDa isoform, CDK11 p58 , is mitosis‐specific and a 46 kDa isoform, CDK11 p46 , is apoptosis‐specific . Similar to other members of the CDK family, CDK11 takes part in both cell cycle control and RNA transcription regulation.…”

“…A 58 kDa isoform, CDK11 p58 , is mitosis-specific and a 46 kDa isoform, CDK11 p46 , is apoptosis-specific. 90,91 Similar to other members of the CDK family, CDK11 takes part in both cell cycle control and RNA transcription regulation. Cyclin-dependent kinase 11 associates with cyclin L, directly binding to various splicing factors and playing a critical role in pre-mRNA splicing.…”

Silencing the roadblocks to effective triple-negative breast cancer treatments by siRNA nanoparticles

“…CDK11 and CK2 are two well-established molecular players that mediate cancer cell growth and survival. CDK11 is an atypical CDK that functions in mitosis, transcription, and RNA splicing, and its elevated expression is observed in TNBCs (Zhou, et al 2016). CK2 is a Ser/Thr protein kinase that phosphorylates numerous substrates that function in cell biology processes such as transcription, cell cycle regulation, apoptosis, and others (Meggio and Pinna 2003).…”

CDK11 safeguards the identity of human embryonic stem cells via fine‐tuning signaling pathways

“…There are three main isoforms of CDK11: CDK11 p110 , CDK11 p58 , and CDK11 p46 . The CDK11 p110 isoform is encoded by the full-length CDK11 messenger RNA (mRNA) which contains an internal ribosome entry site (IRES), and CDK11 p58 can be generated from this IRES site during the G2/M phase of the cell cycle (Cornelis et al, 2000;Zhou, Shen, Hornicek, Kan, & Duan, 2016). The CDK11 p46 isoform is produced from CDK11 p110 and CDK11 p58 after Caspase 1 or 3 cleavage in response to apoptotic signaling (Ariza, Broome-Powell, Lahti, Kidd, & Nelson, 1999;Beyaert et al, 1997;Lahti, Xiang, Heath, Campana, & Kidd, 1995;Tang, Gururajan, & Kidd, 1998).…”

“…Recent studies also indicate a role of CDK11 in human cancers (Zhou et al, 2016). Despite these studies, the function of CDK11 in hESCs remains unknown.…”