p19 INK4d overexpression 293T lysate (whole cell)

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

P19 INK4d also known as CDKN2D is a cyclin-dependent kinase inhibitor with a molecular weight of approximately 19 kDa. It belongs to the INK4 family of proteins and primarily functions to inhibit cyclin-dependent kinases (CDK4 and CDK6) playing an important role in cell cycle regulation by halting the cell cycle in the G1 phase. p19 INK4d is expressed in various tissues including the brain and endocrine organs highlighting its widespread physiological importance. The inhibition of CDK4/6 leads to the prevention of uncontrolled cell proliferation which is a hallmark of cancer.

Biological function summary

The p19 protein exerts its effects by tightly binding to CDK4 and CDK6 forming a complex that impedes their kinase activity. This interaction results in the prevention of the phosphorylation of the retinoblastoma protein (pRb) a critical step required for cell cycle progression from G1 to S phase. In doing so p19 INK4d maintains cellular growth control and prevents the transition into unchecked cell division. The regulation of pRb is vital for the prevention of cancerous growth as phosphorylated pRb releases E2F transcription factors that drive S phase entry and DNA synthesis.

Pathways

The activity of p19 INK4d influences the retinoblastoma (Rb) pathway one of the major pathways governing cell cycle control. The Rb pathway regulates the transcriptional repression of E2F target genes associated with cell cycle progression. Besides its interaction with Rb p19 INK4d is also connected with the p53 pathway which oversees cellular responses to DNA damage and stress. This links p19 INK4d indirectly to proteins like the MDM2 and p21 where these pathways intersect to coordinate cell cycle arrest mechanisms.

Dysregulation or mutations in p19 INK4d relate to certain cancers such as glioblastoma and sarcoma. Alterations impacting the function or expression levels of this protein can bypass its inhibitory role on CDK4/6 facilitating unrestrained cell proliferation. Moreover the p19 protein's connection to the retinoblastoma protein implicates it in diseases where Rb function is compromised as seen in some retinoblastomas. Understanding these relationships helps in elucidating the role of p19 INK4d in tumorigenesis and potentially offers insight into therapeutic interventions targeting the CDK4/6 axis in cancer treatment.